Unit 6.ppt

UNIT 6
CELL MECHANISMS
Cell cycle events - cyclins, cyclindependant kinases, inhibitors;
Cellular mechanisms of developnient in animals - gametogenesis,
blastulation, gastrulation, neurulation and somite formation;
Mechanisms involved in cell determination and differentiation; Cell
senescence, apoptosis and necrosis and Autophagy.
DEEPAK P

INTRODUCTION:
• The cell cycle is the sequence of events that a cell
undergoes from the moment it's formed until it divides
into two daughter cells.
• It's a fundamental process in biology, essential for growth,
development, and tissue repair.
• The cell cycle consists of phases, including interphase,
mitosis (M phase), and cytokinesis.

INTERPHASE:
• Interphase is the longest phase of the cell cycle,
accounting for about 90% of the cycle's duration.
• It's divided into three subphases: G1 (Gap 1), S
(Synthesis), and G2 (Gap 2).

G1 PHASE:
• G1 is the first phase of interphase.
• During G1, the cell grows in size, accumulates energy, and
performs normal metabolic activities.
• It prepares for DNA replication, which happens in the next
phase.

S PHASE:
• S phase stands for Synthesis phase.
• DNA replication occurs during S phase, resulting in the
duplication of the cell's genetic material.
• After S phase, the cell has two complete sets of
chromosomes.

G2 PHASE:
• G2 is the last phase of interphase.
• During G2, the cell continues to grow and prepare for cell
division (mitosis).
• Organelles are replicated, and the cell checks for DNA
errors or damage.

MITOSIS (M PHASE):
• Mitosis is the phase of cell division.
• It ensures that each daughter cell receives an identical set
of chromosomes.
• Mitosis consists of several stages: prophase, metaphase,
anaphase, and telophase.

PROPHASE:
• Chromatin condenses into visible
chromosomes.
• The nuclear envelope begins to break
down.
• Spindle fibers form, extending from
the centrosomes to the
chromosomes.

METAPHASE:
• Chromosomes align at the cell's
equator, known as the metaphase
plate.
• Spindle fibers attach to the
centromeres of each chromosome.
• This alignment ensures that each
daughter cell will receive the same
number and type of chromosomes.

ANAPHASE:
• Sister chromatids (two identical copies
of each chromosome) are pulled apart
by the spindle fibers.
• Chromatids move toward opposite
poles of the cell.
• This stage ensures that each daughter
cell will have a complete set of
chromosomes.

TELOPHASE:
• Chromatids reach opposite poles
and begin to de-condense into
chromatin.
• A new nuclear envelope forms
around each set of chromosomes,
creating two distinct nuclei.
• Mitosis is nearly complete.

CYTOKINESIS:
• Cytokinesis is the final step of the cell cycle.
• It involves the division of the cytoplasm and
organelles between the two daughter cells.
• In animal cells, a contractile ring of actin
filaments pinches the cell's membrane,
creating two separate cells.
• In plant cells, a cell plate forms, ultimately
dividing the cell into two.

CYCLINS: KEY REGULATORS OF THE CELL CYCLE
• Cyclins are a family of proteins that play a crucial
role in regulating the progression of the cell cycle.
• They were discovered in the 1980s and are named
for their cyclical, periodic rise and fall in
concentration during the cell cycle.

• Types of Cyclins:
• G1 Cyclins:
• These cyclins are associated with the G1 phase of the cell cycle.
• G1 cyclins promote the cell's entry into the S phase, where DNA replication occurs.
• S Cyclins:
• These cyclins are present during the S phase.
• They are responsible for initiating and controlling DNA synthesis.
• G2 Cyclins:
• G2 cyclins are found in the G2 phase of the cell cycle.
• They facilitate the cell's preparation for mitosis (M phase).
• M Cyclins:
• M cyclins play a critical role in the progression through mitosis (M phase).
• They regulate the events of mitosis, including chromosome condensation and
segregation.

CYCLIN-DEPENDENT KINASES (CDKS):
• Cyclins do not have enzymatic activity
themselves but rather bind to and
activate specific enzymes called cyclin-
dependent kinases (CDKs).
• CDKs are serine/threonine kinases that
phosphorylate target proteins to
control various cell cycle events.

CYCLIN-CDK COMPLEXES:
• Cyclin-CDK complexes are
formed when cyclins bind to
their corresponding CDKs.
• The activity of these complexes
is tightly regulated and
determines the progression of
the cell cycle.

CELL CYCLE REGULATION BY CYCLINS:
• Cyclin-CDK complexes act as molecular switches,
phosphorylating specific proteins involved in cell cycle
regulation.
• These phosphorylation events control critical checkpoints in
the cell cycle, ensuring that each phase is completed before
the cell progresses to the next.
• Examples of regulated processes include DNA replication,
centrosome duplication, and the initiation of mitosis.

CYCLIN DEGRADATION:
• The concentration of cyclins in the cell rises and falls in a
cyclical manner.
• This cyclic behavior is due to the controlled degradation of
cyclins.
• Ubiquitin-proteasome machinery targets cyclins for
degradation at specific points in the cell cycle.
• Cyclin degradation leads to the inactivation of CDKs, allowing
the cell to exit a particular phase.

ROLE IN CELL CYCLE CHECKPOINTS:
• Cyclins and CDKs are involved in various cell cycle
checkpoints, such as the G1 checkpoint, G2 checkpoint,
and spindle checkpoint.
• These checkpoints ensure that the cell has properly
completed the necessary processes before advancing
through the cell cycle.

CLINICAL IMPLICATIONS:
• Dysregulation of cyclin-CDK complexes can lead to
various diseases, including cancer.
• In cancer, mutations or overexpression of cyclins or
CDKs can result in uncontrolled cell division.
• Targeting cyclin-CDK complexes has become a
therapeutic approach in cancer treatment.

ROLE OF CDKS IN THE CELL CYCLE:
• G1 Phase:
• In early G1 phase, CDK4 and CDK6 form complexes with D-type
cyclins (e.g., cyclin D).
• These complexes regulate the G1 checkpoint, allowing the cell to
enter the S phase when conditions are favorable.
• S Phase:
• Cyclin E binds to CDK2, driving the cell into the S phase, where DNA
synthesis occurs.

ROLE OF CDKS IN THE CELL CYCLE:
• G2 Phase:
• Cyclin A binds to CDK2, contributing to the preparation of the cell for
mitosis (G2 phase).
• M Phase (Mitosis):
• Cyclin B binds to CDK1 (also known as Cdc2), initiating the onset of
mitosis.
• This cyclin-CDK complex regulates the events of mitosis, including
chromosome condensation, alignment, and separation.

• Cell Cycle Checkpoints and CDKs:
• CDKs play a vital role in regulating cell cycle checkpoints,
ensuring the cell proceeds through the cycle only when
conditions are appropriate.
• Examples include the G1 checkpoint, G2 checkpoint, and spindle
checkpoint in mitosis.
• Regulation of CDK Activity:
• CDK activity is tightly regulated by other proteins called CDK
inhibitors (CKIs).
• CKIs can block the binding of cyclins to CDKs or directly inhibit
CDK kinase activity.

CELL CYCLE EVENT INHIBITORS: REGULATING CELL CYCLE
PROGRESSION
• Cell cycle event inhibitors are molecules that regulate the
progression of the cell cycle by controlling key
checkpoints and processes.
• These inhibitors play a crucial role in maintaining cellular
homeostasis, preventing uncontrolled cell division, and
ensuring DNA integrity.

TYPES OF CELL CYCLE EVENT INHIBITORS:
• Cyclin-Dependent Kinase Inhibitors (CKIs):
• CKIs are proteins that can bind to and inhibit cyclin-dependent kinases (CDKs),
which are key regulators of the cell cycle.
• They are categorized into two classes: INK4 (Inhibitors of CDK4) and Cip/Kip
inhibitors.
• Tumor Suppressor Proteins:
• Tumor suppressor proteins like p53 and Rb (Retinoblastoma protein) play a
significant role in inhibiting cell cycle progression.
• For instance, p53 can halt the cell cycle at the G1 checkpoint to allow DNA repair or
induce apoptosis if the DNA damage is severe.

TYPES OF CELL CYCLE EVENT INHIBITORS:
• Checkpoints and DNA Repair Proteins:
• Proteins involved in the checkpoints and DNA repair
mechanisms can act as inhibitors.
• For example, the ATM and ATR kinases detect DNA damage
and initiate signaling pathways that inhibit cell cycle
progression until the damage is repaired.
*Ataxia-Telangiectasia mutated *ATM- and Rad3-related

FUNCTION AND MECHANISMS OF CELL CYCLE
EVENT INHIBITORS:
• Halting Progression at Checkpoints:
• Cell cycle inhibitors can arrest cell cycle progression at checkpoints to allow time
for necessary cellular processes or repairs.
• For instance, p53 activation can halt the cell cycle at the G1 checkpoint to
facilitate DNA repair.
• Preventing CDK Activity:
• CKIs directly inhibit CDKs, preventing them from phosphorylating target proteins
and initiating cell cycle events.
• This inhibition prevents cells from entering the S phase or proceeding to mitosis.

FUNCTION AND MECHANISMS OF CELL CYCLE
EVENT INHIBITORS:
• Initiating Apoptosis:
• Some cell cycle inhibitors can induce programmed cell death
(apoptosis) if cellular damage is too severe to be repaired.
• This is a protective mechanism to eliminate cells with
potentially harmful genetic alterations.

• Role in Disease and Cancer:
• Dysregulation of cell cycle event inhibitors can lead to uncontrolled cell division and is
is often associated with cancer.
• Mutations or inactivation of tumor suppressor proteins (e.g., p53 or Rb) can lead to
unrestrained cell proliferation.
• Inhibitors targeting CDKs have been developed as cancer therapies to restore control
over the cell cycle in cancer cells.
• Clinical Applications:
• Cell cycle event inhibitors, especially CDK inhibitors, have been developed and used as
as anticancer drugs.
• These inhibitors aim to selectively target cancer cells, disrupting their ability to divide
and grow uncontrollably while sparing normal cells.

CELLULAR MECHANISMS OF DEVELOPMENT IN ANIMALS
• Cellular mechanisms of development in animals are highly
complex and orchestrated processes that ensure the
growth, differentiation, and organization of cells into
functional tissues and organs.
• These mechanisms involve various cellular processes,
signaling pathways, and genetic regulation.

• Cell Division:
• The process of cell division, primarily through mitosis, plays a
fundamental role in animal development.
• It ensures the production of a sufficient number of cells for tissue and
organ formation.
• Cell Differentiation:
• Cell differentiation is the process by which unspecialized cells (stem cells)
become specialized into various cell types with specific functions.
• Differentiation is governed by gene expression patterns and signaling
pathways.

• Cell Signaling:
• Cell-to-cell communication through signaling pathways is crucial for pattern
formation and cell differentiation.
• Signaling molecules, such as growth factors and morphogens, guide cells to
adopt specific fates and positions within the developing embryo.
• Morphogenesis:
• Morphogenesis refers to the shaping and structuring of tissues and organs
during development.
• It involves processes like cell migration, cell adhesion, and tissue remodeling.

• Apoptosis (Programmed Cell Death):
• Apoptosis is a tightly regulated process of programmed cell death
that is essential for sculpting and refining developing tissues.
• It removes excess or unwanted cells, helping to create precise
structures.
• Germ Cell Formation:
• Germ cells, which give rise to eggs and sperm, are specified during
development.
• The formation and migration of germ cells are crucial for
reproduction.

• Notch-Delta Signaling:
• The Notch-Delta signaling pathway plays a role in lateral inhibition,
where neighboring cells communicate to determine their distinct cell
fates.
• It helps establish a regular pattern of cell differentiation.
• Hedgehog Signaling:
• The Hedgehog signaling pathway is involved in controlling cell
differentiation, tissue patterning, and limb development in vertebrates.
• Dysregulation of this pathway can lead to developmental disorders
and cancer.

• Homeobox Genes (Hox Genes):
• Homeobox genes are regulatory genes that play a role in establishing the
body plan and segmental identity during development.
• They control the positioning and differentiation of cells along the anterior-
posterior axis.
• Transcription Factors and Gene Regulation:
• The activation and repression of specific genes through transcription
factors are central to cell fate determination and differentiation.
• Complex gene regulatory networks guide cellular decisions during
development.

• Cell-Cell Adhesion and Extracellular Matrix (ECM):
• Cells adhere to one another and to the extracellular matrix
through adhesion molecules, influencing tissue
organization and morphogenesis.
• Epigenetic Regulation:
• Epigenetic modifications, such as DNA methylation and
histone modifications, can stably alter gene expression
patterns and are critical for cell differentiation.

• Stem Cells:
• Stem cells contribute to tissue growth and repair during
development and throughout an organism's life.
• They have the capacity to self-renew and differentiate into
specialized cell types.
• Cellular Membrane Dynamics:
• Membrane dynamics are essential for processes like cell migration,
neurite outgrowth, and tissue folding during development.

GAMETOGENESIS
• Gametogenesis is the process by which specialized sex
cells, called gametes, are produced.
• In animals, gametogenesis occurs through a series of
complex cellular events that result in the formation of
either sperm (spermatogenesis) or eggs (oogenesis).

INTRODUCTION:
• Gametes are reproductive cells that are essential for sexual
reproduction in animals.
• In most animals, there are two types of gametes: sperm
(male) and eggs (female).
• Gametogenesis is the process by which diploid germ cells
(spermatogonia or oogonia) undergo specialized divisions
to form haploid gametes (sperm or eggs).

Human sperm cell
Fish sperm cell
Rodents sperm cell

SPERMATOGENESIS (MALE GAMETOGENESIS):
• Spermatogonia (Diploid Cells):
• The process of spermatogenesis begins with diploid spermatogonia,
located in the testes.
• Meiosis I:
• Spermatogonia undergo meiosis I, resulting in the formation of two
haploid daughter cells called secondary spermatocytes.
• Meiosis II:
• Each secondary spermatocyte undergoes meiosis II, yielding four haploid
spermatids.

SPERMATOGENESIS (MALE GAMETOGENESIS):
• Spermiogenesis:
• Spermatids then undergo spermiogenesis, a process of cellular
differentiation.
• During spermiogenesis, the round spermatids transform into
elongated, mature sperm cells (spermatozoa).
• Sperm Maturation:
• The newly formed sperm undergo maturation processes in the
epididymis, acquiring the ability to swim and fertilize an egg.

OOGENESIS (FEMALE GAMETOGENESIS):
• Oogonia (Diploid Cells):
• Oogenesis begins with diploid oogonia in the ovaries.
• Meiosis I:
• Oogonia undergo meiosis I, producing a larger primary
oocyte and a smaller polar body.
• Meiosis I typically begins during fetal development but
halts until puberty.

OOGENESIS (FEMALE GAMETOGENESIS):
• Meiosis II:
• At puberty, primary oocytes resume meiosis and complete
meiosis I, resulting in a secondary oocyte and another polar
body.
• The secondary oocyte is released from the ovary during
ovulation and arrested in metaphase of meiosis II.
• Fertilization:
• If fertilization occurs, the secondary oocyte completes meiosis II,
forming a mature ovum (egg) and a second polar body.

KEY DIFFERENCES BETWEEN SPERMATOGENESIS AND
OOGENESIS:
• Spermatogenesis results in the production of four functional sperm
cells, whereas oogenesis typically yields one egg and multiple polar
bodies.
• Spermatogenesis occurs continuously from puberty onwards, while
oogenesis is limited, with most primary oocytes arrested in meiosis
until puberty.
• The final products of spermatogenesis (sperm) are small, mobile,
and designed for fertilization, while the final product of oogenesis
(egg) contains nutrient stores and organelles for embryonic
development.

Regulation:
• Gametogenesis is regulated by various hormones, including follicle-
stimulating hormone (FSH) and luteinizing hormone (LH) in both
males and females.
• In females, estrogen and progesterone play essential roles in
regulating oogenesis.
Significance:
• Gametogenesis is essential for sexual reproduction, as it produces
the specialized cells necessary for fertilization.
• Genetic diversity is generated through the independent assortment
of chromosomes during meiosis, contributing to the variation within
species.

BLASTULATION
• Blastulation is a crucial stage in the early embryonic
development of animals, particularly in those that
undergo a process called blastula formation.
• It is a critical step that follows fertilization and the
formation of a zygote.
• During blastulation, the zygote undergoes a series of cell
divisions and rearrangements, leading to the formation of
a multicellular structure known as the blastula.

• Zygote Formation: Blastulation occurs after fertilization when a
sperm cell fuses with an egg cell to form a zygote.
• Cleavage: The zygote undergoes rapid cell divisions called cleavage.
Cleavage divisions are typically mitotic and result in a multicellular
embryo without a significant increase in the overall size of the
embryo.
• Formation of Blastomeres: During cleavage, the zygote divides into
smaller cells called blastomeres. These blastomeres are totipotent,
meaning they have the potential to give rise to all cell types in the
organism.

• Morula Stage: As cleavage continues, the embryo transforms into a
solid, spherical mass of cells known as the morula. The morula is a
compact structure made up of blastomeres.
• Blastocyst Formation: Further cleavage leads to the formation of a
blastocyst. In mammals, this is a significant development. The
blastocyst consists of two main parts: the inner cell mass (ICM) and
the outer layer of cells called the trophoblast.

• Inner Cell Mass: The ICM contains cells that will eventually give rise to
the embryo itself. These cells are pluripotent, meaning they can
differentiate into various cell types but not all, unlike the totipotent
blastomeres.
• Trophoblast: The trophoblast will develop into extraembryonic
structures, including the placenta and amniotic sac, supporting the
developing embryo.
• Blastocoel: The blastocyst also contains a fluid-filled cavity called the
blastocoel. This cavity allows the embryo to become a hollow, fluid-
filled sphere.

• Implantation: After blastulation, the blastocyst undergoes
a process called implantation, where it attaches to the
uterine lining in mammals or another appropriate location
in non-mammalian species.
• Continuation of Development: Following implantation, the
embryo continues to develop, and various cell layers give
rise to different tissues and organs during the later stages
of embryogenesis.

GASTRULATION
• Gastrulation is a fundamental and highly orchestrated
process during the embryonic development of animals.
• It involves the transformation of a blastula (a hollow, fluid-
filled ball of cells) into a gastrula, which has distinct layers
of embryonic tissues.
• Gastrulation sets the stage for the formation of various
organ systems and body structures in the developing
organism.

• Blastula Formation: Gastrulation follows the blastulation
stage, where the embryo is a hollow sphere consisting of
an outer layer of cells (trophoblast in mammals) and an
inner cell mass.
• Initiation: Gastrulation begins with the formation of a
region called the blastopore. The blastopore is an
invagination or indentation in the blastula.

• Three Germ Layers: Gastrulation results in the formation of
three primary germ layers:
• Ectoderm: The outermost layer, which gives rise to the skin,
nervous system, and sense organs.
• Mesoderm: The middle layer, responsible for developing into
muscles, bones, circulatory system, and various internal organs.
• Endoderm: The innermost layer, which will become the lining of
the digestive and respiratory tracts, as well as certain internal
organs.

• Formation of the Primitive Streak: In vertebrates, such as
humans, the primitive streak is a structure that appears
during gastrulation. Cells migrate toward the primitive
streak and ingress into the embryo to establish the three
germ layers.
• Cell Movement: Cells at the surface of the blastula
undergo coordinated movements, including invagination,
involution, and ingression, to create the three germ layers.
• Pattern Formation: Gastrulation is a crucial step in pattern
formation, as it establishes the spatial organization of
tissues and organs in the developing embryo.

• Inductive Signals: Various signaling molecules, such as
growth factors and morphogens, play essential roles in
guiding cells during gastrulation, determining their future
fates.
• Continuation of Development: After gastrulation,
organogenesis begins, where the germ layers give rise to
specific tissues and organs. This process continues
throughout embryonic development.
• Importance: Gastrulation is a highly conserved and critical
process in animal development. It sets the foundation for
the formation of diverse body structures and is essential
for the proper development of multicellular organisms.

NEURULATION
• Neurulation is a critical process during the early embryonic
development of vertebrate animals, including humans.
• It involves the formation of the neural tube, which eventually
gives rise to the central nervous system (CNS), including the
brain and spinal cord.
• Neurulation is a tightly regulated and highly organized
process that sets the foundation for the development of the
nervous system.

• Early Embryonic Stage: Neurulation takes place during the early
stages of embryonic development, typically after gastrulation.
• Initiation: The process begins with the formation of the neural
plate, a specialized region of the embryonic ectoderm. This
region is initially flat and will eventually transform into the
neural tube.
• Neural Plate: The neural plate is a thickened region of cells in the
dorsal (top) part of the embryo. It arises from specific signaling
events involving proteins like BMPs (bone morphogenetic
proteins) and noggin.

• Elevation and Fusion: The neural plate undergoes a process
called elevation, where it folds up and forms two parallel ridges
known as the neural folds. These neural folds eventually come
together and fuse along the midline to create the neural tube.
• Formation of the Neural Tube: Once fused, the neural tube forms
a hollow, tube-like structure. The cells along the outer surface of
the neural tube will become the skin and other tissues, while the
inner cells will give rise to the entire central nervous system.

• Closure: Neural tube closure occurs first in the middle and
proceeds both cranially (toward the head) and caudally
(toward the tail) until the entire neural tube is sealed.
Failure of proper closure can lead to neural tube defects.
• Development of the Brain and Spinal Cord: After closure,
the neural tube differentiates into various regions,
ultimately giving rise to the brain and spinal cord. The
anterior part of the tube becomes the brain, while the
posterior part develops into the spinal cord.

• Critical Period: Neurulation is a critical period during embryonic
development. Any disruptions or abnormalities during this process can lead
to severe congenital neural tube defects, such as spina bifida or
anencephaly.
• Genetic and Environmental Factors: Proper neurulation is influenced by both
genetic factors (including specific genes) and environmental factors (such as
folate intake). Folate supplementation is essential during pregnancy to
reduce the risk of neural tube defects.
• Neurulation is a fundamental and highly regulated process that lays the
foundation for the development of the nervous system in vertebrate
animals. It exemplifies the complex and precise coordination of cellular and
molecular events during embryonic development.

SOMITE FORMATION
• Somite formation is a critical process during the
embryonic development of vertebrate animals, including
humans.
• Somites are segmented blocks of mesodermal tissue that
give rise to various structures in the body, including the
vertebrae, muscles, and dermis of the skin.

• Embryonic Mesoderm: During early embryonic development,
the mesoderm, one of the three primary germ layers (along
with ectoderm and endoderm), undergoes a process called
somitogenesis to form somites.
• Initiation: Somitogenesis begins during the development of
the neural tube, which is formed during neurulation. It occurs
in the paraxial mesoderm, a region adjacent to the neural
tube.
• Segmentation: The paraxial mesoderm undergoes
segmentation, leading to the formation of discrete, paired
blocks of tissue known as somites. These somites are
organized in a regular and linear pattern along the length of

• Progressive Formation: Somite formation is progressive, with new somites
forming sequentially from anterior (head) to posterior (tail) regions of the
embryo. This process continues over several days.
• Hox Gene Expression: The formation and regional identity of somites are
regulated by the expression of Hox genes, which are responsible for
specifying the identity of each somite along the anterior-posterior axis. The
expression of specific Hox genes determines the fate of somites and the
structures they will give rise to.
• Differentiation: Somites eventually differentiate into various tissues and
structures:
• Sclerotome: Forms the vertebrae and rib cartilage.
• Myotome: Gives rise to the muscles of the body.
• Dermatome: Forms the dermis of the skin.
• Other derivatives: Somites also contribute to tendons, ligaments, and other connective

• Importance: Somite formation is crucial for the development of the
segmented body plan seen in vertebrates, including humans. The
segmented arrangement of somites along the vertebral column is
responsible for the distinct regions of the spine and the formation of
segmental muscles.
• Disorders: Abnormalities or disruptions in somite formation can lead
to congenital disorders, such as congenital scoliosis or other skeletal
and muscular anomalies.
• Somite formation is a highly regulated and intricate process that
ensures the proper development of the vertebrate body plan. The
sequential formation of somites and their differentiation into specific
tissues and structures are essential for the functional organization of
the developing embryo.

MECHANISMS INVOLVED IN CELL DETERMINATION
AND DIFFERENTIATION
• Cell determination and differentiation are fundamental
processes in embryonic development, tissue homeostasis,
and the formation of various cell types in multicellular
organisms.
• These processes are tightly regulated and involve a
combination of genetic, molecular, and cellular
mechanisms.

•Gene Expression and Regulation:
• Transcription Factors: Transcription factors are
proteins that regulate gene expression by binding to
specific DNA sequences. They play a central role in
determining cell fate by activating or repressing
target genes.
• Cell-Type-Specific Genes: Different cell types express
unique sets of genes, and the selective activation or
repression of these genes is a crucial aspect of cell
determination and differentiation.

•Signaling Pathways:
• Cell Signaling: Interactions between neighbouring
cells and extracellular signals activate intracellular
signalling pathways. These pathways can trigger
changes in gene expression and cellular behaviour.
• Morphogens: Morphogens are signalling molecules
that create concentration gradients in developing
tissues. These gradients provide positional
information and guide cells to adopt specific fates
based on their location.

• Epigenetic Modifications:
• DNA Methylation: Methylation of DNA can silence or
activate genes, influencing cell fate. Patterns of DNA
methylation can be heritable and play a role in cellular
memory.
• Histone Modifications: Chemical modifications of histone
proteins in chromatin can alter the accessibility of genes.
Acetylation, methylation, and phosphorylation are examples
of histone modifications that affect gene expression.

• Cell-Cell Interactions:
• Notch Signaling: The Notch pathway is involved in cell fate
determination and differentiation by mediating interactions
between adjacent cells. It influences cell fate decisions
during processes like neurogenesis and tissue patterning.
• Cell-Cell Adhesion: Cell adhesion molecules, such as
cadherins, mediate cell-cell interactions. These molecules
can influence tissue organization and cell differentiation.

• MicroRNAs (miRNAs):
• miRNA Regulation: MicroRNAs are small RNA molecules that can post-
transcriptionally regulate gene expression by binding to messenger RNA (mRNA).
They play a role in fine-tuning gene expression during development.
• Asymmetric Cell Division:
• Stem Cell Maintenance: Asymmetric cell division is a process where a single cell
divides into two daughter cells with distinct fates. This mechanism is crucial for
maintaining stem cell populations and generating differentiated cell types.
• Cell Plasticity:
• Cell Fate Changes: In some cases, cells can change their fate or differentiate into
different cell types under specific conditions. This phenomenon is known as cell
plasticity and is observed in processes like tissue regeneration.

• Cell Fate Determinants:
• Cytoplasmic Determinants: In some species, maternal factors are
asymmetrically distributed in the egg during early development.
These determinants can influence cell fate in the developing embryo.
• Environmental Influences:
• Microenvironment: The local cellular and extracellular environment
can influence cell determination and differentiation. Factors such as
oxygen levels, nutrient availability, and mechanical forces can impact
cell fate.
• Feedback Loops:
• Positive and Negative Feedback: Feedback mechanisms involving
gene expression and signaling pathways can reinforce or inhibit cell
fate decisions, ensuring robustness and precision in development.

CELL SENESCENCE
• Cell senescence refers to a state of irreversible cell cycle
arrest in which cells lose their ability to divide and
proliferate.
• Senescent cells remain metabolically active but can no
longer replicate or contribute to tissue growth and repair.
• This process is a natural part of aging and serves as a
protective mechanism against uncontrolled cell growth
and potential cancer development.

• Cell Cycle Arrest: Senescent cells are unable to progress
through the cell cycle. They are typically arrested in the G1
phase, just before entering the S phase, where DNA
replication occurs.
• Permanent State: Cell senescence is considered an
irreversible state. Once a cell becomes senescent, it cannot
resume normal cell division.
• Morphological Changes: Senescent cells often undergo
changes in shape and size. They may become enlarged and
flatten out.

• Increased Senescence-Associated β-Galactosidase (SA-β-Gal): One
characteristic feature of senescent cells is increased expression of an
enzyme called senescence-associated β-galactosidase (SA-β-Gal).
Detection of SA-β-Gal activity is a common marker for senescence.
• DNA Damage Response: Senescence can be triggered by various forms of
DNA damage, such as telomere shortening, oxidative stress, or oncogene
activation. Cells sense this damage and initiate a DNA damage response,
leading to senescence.
• Secretory Phenotype (SASP): Senescent cells often exhibit a pro-
inflammatory secretory phenotype known as the senescence-associated
secretory phenotype (SASP). They release various inflammatory cytokines,
growth factors, and proteases, which can influence nearby cells and
tissues.

FUNCTIONS AND SIGNIFICANCE OF CELL
SENESCENCE:
• Tumor Suppression: One of the primary functions of cell senescence is
to act as a tumor suppressor mechanism. When cells accumulate
genetic mutations or damage that could lead to uncontrolled cell
division (cancer), they may undergo senescence instead, preventing
cancer development.
• Tissue Repair: Senescence can also play a role in tissue repair and
wound healing. Senescent cells can secrete factors that recruit immune
cells and promote tissue regeneration.

• Aging: As organisms age, the accumulation of senescent cells in
tissues is believed to contribute to the aging process.
Senescent cells can disrupt tissue function and promote
inflammation.
• Immune Surveillance: The immune system can recognize and
remove senescent cells through a process called
immunosurveillance. However, with aging, the efficiency of this
surveillance may decrease.
• Senolytics: Researchers are exploring senolytic drugs that can
selectively target and eliminate senescent cells. This approach is
is being investigated for its potential to delay age-related
diseases and improve healthspan.

APOPTOSIS
• Apoptosis, often referred to as programmed cell death or
cell suicide, is a highly regulated and controlled process of
cell elimination that occurs in multicellular organisms.
• It plays crucial roles in various physiological processes,
including tissue development, immune response, and the
maintenance of tissue homeostasis.

• Highly Regulated: Apoptosis is a tightly regulated process governed by a
complex network of genes and signaling pathways. It is carefully
orchestrated to ensure that cells are removed without causing
inflammation or damage to neighboring cells.
• Cell Shrinkage: Apoptotic cells typically undergo shrinkage, resulting in a
reduction in cell size.
• Membrane Blebbing: During apoptosis, the cell membrane forms
characteristic protrusions or blebs.
• Chromatin Condensation: The chromatin within the nucleus of apoptotic
cells condenses, leading to changes in nuclear morphology.

• DNA Fragmentation: One of the hallmark features of apoptosis is
DNA fragmentation, resulting in the characteristic "DNA ladder"
pattern seen on gel electrophoresis.
• Phagocytosis: Apoptotic cells release signals that attract phagocytic
immune cells (e.g., macrophages) to engulf and digest the apoptotic
bodies. This process is typically anti-inflammatory and does not
cause an immune response.

ROLES OF APOPTOSIS
• Development: Apoptosis plays a crucial role in the development of tissues
and organs. For example, during the formation of fingers and toes in
embryos, the cells between the digits undergo apoptosis, allowing for the
separation of individual digits.
• Tissue Homeostasis: Apoptosis helps maintain tissue homeostasis by
eliminating damaged, infected, or unwanted cells. It is an essential
mechanism for replacing old or dysfunctional cells with new ones.
• Immune Response: Apoptosis is involved in immune responses. Infected or
cancerous cells can undergo apoptosis to prevent the spread of infection
or cancer.

• Preventing Autoimmunity: Apoptosis helps prevent autoimmune
responses by eliminating self-reactive immune cells and cells
expressing abnormal antigens.
• Cancer Suppression: Dysregulation of apoptosis can contribute to
cancer development. Normally, cells with damaged DNA or
mutations undergo apoptosis to prevent the proliferation of
potentially cancerous cells.
• Chemotherapy and Radiation: Cancer treatments such as
chemotherapy and radiation therapy induce apoptosis in cancer
cells, leading to their death.

REGULATION OF APOPTOSIS
• Intrinsic Pathway: Also known as the mitochondrial pathway, it is
regulated by mitochondrial factors and is triggered by cellular
stress, such as DNA damage or loss of survival signals.
• Extrinsic Pathway: Initiated by external death signals, such as
binding of death ligands (e.g., Fas ligand) to death receptors on the
cell surface.
• Caspases: Key protease enzymes called caspases play a central role
in apoptosis by cleaving specific cellular proteins, leading to cell
death.

REGULATION OF APOPTOSIS
• Bcl-2 Family: Proteins of the Bcl-2 family regulate
mitochondrial permeability and control the release of pro-
apoptotic factors.
• Survival Signals: Growth factors and survival signals from
neighboring cells can inhibit apoptosis.

NECROSIS
• Necrosis is a form of cell death that occurs as a
result of cellular injury, trauma, or disease.
• Unlike apoptosis, which is a highly regulated and
controlled process, necrosis is a form of
unregulated cell death that typically results from
severe damage to cells or tissues.

CHARACTERISTICS OF NECROSIS:
• Unregulated Process: Necrosis is characterized by its unregulated
and chaotic nature. It is not a programmed or controlled process
like apoptosis.
• Cell Swelling: Necrotic cells often swell due to the influx of water
and ions. This results in the enlargement of affected cells.
• Cell Membrane Disruption: Necrosis leads to the disruption of the
cell membrane, causing the release of intracellular contents,
including enzymes and cell components, into the extracellular
space. This can trigger inflammation.

CHARACTERISTICS OF NECROSIS:
• Inflammation: Necrosis typically provokes an inflammatory
response, as the release of cellular contents can stimulate the
immune system and lead to the recruitment of immune cells to the
site of necrosis.
• Nuclear Changes: In necrotic cells, the nucleus often undergoes
changes such as karyolysis (dissolution of the nucleus), pyknosis
(nuclear shrinkage), and karyorrhexis (nuclear fragmentation).
• Multiple Causes: Necrosis can result from various causes, including
physical injury, infection, toxins, lack of blood supply (ischemia), and
chemical exposure.

TYPES OF NECROSIS:
• Coagulative Necrosis: This is the most common type of necrosis and is
characterized by the preservation of tissue architecture. It often occurs in
response to ischemia (lack of blood supply) and is seen in conditions like
myocardial infarction (heart attack).
• Liquefactive Necrosis: In liquefactive necrosis, the affected tissue becomes
liquefied due to the action of enzymes and immune cells. It is commonly
associated with bacterial infections and is often seen in the brain during
abscess formation.
• Caseous Necrosis: This type of necrosis results in a cheese-like, soft, and
granular appearance of the affected tissue. It is commonly found in

TYPES OF NECROSIS:
• Gangrenous Necrosis: Gangrenous necrosis occurs when a significant
portion of tissue undergoes necrosis, often due to a lack of blood supply.
It can be dry (coagulative) or wet (liquefactive) depending on the presence
of bacterial infection.
• Fat Necrosis: Fat necrosis occurs in adipose (fat) tissue and is often
associated with trauma or inflammation. It can result in the formation of
calcium deposits.

AUTOPHAGY
• Autophagy is a cellular process that involves the degradation and
recycling of cellular components, such as organelles and proteins, to
maintain cellular homeostasis and adapt to changing environmental
conditions.
• The term "autophagy" is derived from the Greek words "auto" (self)
and "phagy" (eating), which reflect the process of a cell "self-eating"
to remove damaged or unnecessary cellular material.
• Autophagy plays critical roles in various physiological processes and
is essential for cell survival and overall health.

TYPES OF AUTOPHAGY:
• Macroautophagy: This is the most well-studied form of autophagy and involves
the formation of a double-membrane structure called an autophagosome around
cellular components to be degraded. The autophagosome fuses with a lysosome,
forming an autolysosome, where the contents are degraded by lysosomal
enzymes.
• Microautophagy: In microautophagy, small portions of the cytoplasm or
organelles are directly engulfed by lysosomes, which then digest and recycle the
captured material.
• Chaperone-Mediated Autophagy (CMA): CMA is a highly selective form of
autophagy in which specific proteins are targeted for degradation. A chaperone
protein recognizes a protein with a CMA-targeting motif and transports it to the
lysosome, where it is translocated into the lysosomal lumen and degraded.

FUNCTIONS AND SIGNIFICANCE OF AUTOPHAGY:
• Cellular Quality Control: Autophagy plays a crucial role in maintaining cellular
quality control by removing damaged or malfunctioning organelles (e.g.,
mitochondria), misfolded proteins, and other cellular debris.
• Adaptation to Stress: Autophagy is induced in response to various stresses,
such as nutrient deprivation, oxidative stress, and infections. It helps the cell
adapt to these stressors by providing a source of energy and essential building
blocks.
• Immunity: Autophagy contributes to the immune response by eliminating
intracellular pathogens, such as viruses and bacteria, through a process known
as xenophagy.

• Development: Autophagy is involved in the regulation of tissue development
and differentiation during embryogenesis. It helps shape organs and tissues by
removing unwanted structures.
• Aging and Longevity: Autophagy has been linked to the aging process and
longevity. Enhanced autophagy is associated with increased lifespan in some
model organisms.
• Neurodegenerative Diseases: Dysregulation of autophagy is implicated in
various neurodegenerative diseases, including Alzheimer's disease, Parkinson's
disease, and Huntington's disease. Proper autophagy is essential for the
clearance of toxic protein aggregates.
• Cancer: Autophagy can have both tumor-suppressive and tumor-promoting
effects, depending on the context. It may help cancer cells survive in nutrient-
deprived conditions or contribute to the elimination of damaged cells.

Regulation of Autophagy:
• Autophagy is tightly regulated by a complex network of genes and
and signaling pathways. Key regulators include the mTOR
(mammalian target of rapamycin) pathway, which inhibits
autophagy when active, and various autophagy-related (ATG)
proteins that facilitate the autophagy process.
• Autophagy is a dynamic and essential cellular process that helps
maintain cellular health, adapt to changing conditions, and
contribute to various physiological and pathological processes. Its
regulation and functions continue to be the focus of extensive
research in cell biology and disease.

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