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Development of the branchial arches  Heather Etchevers, Ph.D. INSERM
Relation of face to pharynx frontonasal bud maxillary process mandibular process
Pharyngeal arches are also known as branchial or aortic The embryonic dorsal aortae are paired before later fusing at the midline
Pharyngeal arches The arches are metameric structures numbered 1 to 4 and 6 in humans “ #5” does not exist as a separate entity Each arch is built around the cage of aortic arches between ventral and dorsal aortae Each pair = unique complement of: Muscles and connective tissue Nerves Cartilage (bone for PA1-3) Segment of the branchial arterial tree Endodermal  anlage  to the neck glands
The first aortic arch is the precursor to all pharyngeal arches Ventral view,  human embryonic heart
Rostrocaudal maturation of arches Detrait and Etchevers, 2005
All pharyngeal arch arteries are never present at once Constant remodeling during embryonic life Growth factor guidance of  endothelial cells Immature mural coverage Flow pressures and hemodynamics Obliterated 1st PA Maxillary artery Right dorsal aorta Left dorsal aorta 1st PA 2nd PA 3rd PA 4th PA
Craniofacial evolution MOUTH MOUTH r e t i n a s e l e c t i o n o f N C C G n a t h o s t o m e M O U T H p r o s m e s
Volumes and surfaces Outer, notched ectoderm Inner, pouched-out endoderm Membranes where they meet Mesodermal core of muscle and vascular endothelium Neural crest mesenchyme hindbrain pros PA1 2 3 4 heart
Pouches and grooves 1 2 Persists as tympanic membrane endoderm ectoderm Persists as intratonsillar cleft bpm midbrain 3
Endoderm and vascular development Dorsal aorta Arterial vitelline plexus Endoderm 1 st  pharyngeal pouch Vitelline arteries Pharyngeal arch arteries Internal carotid Umbilical arteries
Endodermal expression of  hypoxia-inducible factor 1  HIF1   is a TF activated under hypoxic/growth conditions It effects transcription of pro-vascular factors such as VEGF, ET-1 Etchevers, 2003
Endodermal derivatives of pouches Pharyngeal endoderm Derivative 1 Epithelium of tympanic cavity and auditory tube 2 Epithelium of tonsil 3 Inferior parathyroid glands and epithelium of thymus 4 Superior parathyroid glands
 
Tongue and salivary glands Contributions from most arches Endoderm and mesoderm First oral anterior 2/3 Second Surface contribution not maintained; tonsillar crypts Third pharyngeal posterior 1/3 Fourth Epiglottis and vicinity The salivary glands are ectodermal ingrowths of the oral cavity that associate with NC mesenchyme
Structural derivatives Pharyngeal Arch Cranial Nerve Muscle derivative Skeletal Derivative 1 Maxillary Trigeminal nerve (V) Superior oblique Abducens Oculomotor muscles Maxillary, palatine, jugal trabecula cranii  1 Mandibular Trigeminal nerve (V) Muscles of mastication Tensor tympanis Digastric (anterior belly) Incus, ant. lig of malleus palatoquadrate Meckel’s cartilage 2  Hyoid Facial nerve (VII) Muscles of facial expression, digastric (posterior belly), styloid Stapes, hyoid bone Reichert’s cartilage 3 Glossopharyngeal nerve (IX) stylopharyngeas Horns of hyoid Thyroid cartilage 4 and 6 Laryngeal branches of vagus nerve (X) Striated muscles of oesophagus Cricoid cartilage
Cartilage derivatives of arches  in 24 wk foetus
Hox  segment identity genes are incompatible with  facial  skeleton Creuzet et al. (2002) Couly et al. 1993
Human embryo aortic arches Courtesy of Next Generation Embryology http://ngembryo.ncl.ac.uk/ngembryo.php
Chicken head vessels are in two sectors
Vascular derivatives Internal/ external jugular Brachiocephalic Subclavian Sinus venosus? Pharyngeal arch Arteries Veins- tentative 1 st  maxillary (shared artery with mandibular) Ophthalmic, ethmoid, ramus superior of stapedial 1 st  mandibular Maxillary, mandibular 2 nd  hyoid Stapedial 3rd Common and internal carotids 4th Right subclavian (R) Aorta (L) 6th Right proximal pulmonary Left proximal pulmonary Ductus arteriosis
The “cardiac” neural crest is a subpopulation of the cephalic crest
Heart participation of NCC is necessary but transitory © K Sulik and coll.
Oculo-auriculo-vertebral spectrum a.k.a. First arch or Goldenhar syndrome, hemifacial microsomia – though can be bilateral Malformation of jaws, ears and face Experimentally induced by hemorrhage of 2 nd  pharyngeal arch Fortuitous genetic mouse model Often overlaps with DiGeorge, VACTERL…
Goldenhar, First arch, hemifacial microsomia, oculo-auriculo-vertebral spectrum (MIM  164210) Axial 1-mm 3D FT-CISS MR image through temporal bones.  Lemmerling et al., AJNR 2000. Universitätsklinikum Jena   semi- circular canals (L) enlarged vestibular aqueduct (R)
Cardiovascular defects in DGS
Congenital vascular anomalies arise from defective arch remodeling Double aortic arch Non-regression of right aortic arch Aberrant right subclavian artery 1% of normal population but 40% of tri 21 or CHD Right aortic arch Retention of the dorsal aorta on right side Ductus arteriosus deflected to right Up to 1/3 of tetralogy of Fallot, 1/10 TGV Interrupted aortic arch Regression of both right and left 4th arch Coarctation of aorta Constriction near normally remodeling ductus arteriosus (6 th  arch)
Main points Pharyngeal arches are metameric structures They each contain all germ layers, each of which contributes to distinct structures for each arch Hox  genes confer identity to differentiate them  like for other metameric structures (eg. somites) not with respect to the facial skeleton Arch, facial and heart development are linked

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Development Of The Branchial Arches

  • 1. Development of the branchial arches Heather Etchevers, Ph.D. INSERM
  • 2. Relation of face to pharynx frontonasal bud maxillary process mandibular process
  • 3. Pharyngeal arches are also known as branchial or aortic The embryonic dorsal aortae are paired before later fusing at the midline
  • 4. Pharyngeal arches The arches are metameric structures numbered 1 to 4 and 6 in humans “ #5” does not exist as a separate entity Each arch is built around the cage of aortic arches between ventral and dorsal aortae Each pair = unique complement of: Muscles and connective tissue Nerves Cartilage (bone for PA1-3) Segment of the branchial arterial tree Endodermal anlage to the neck glands
  • 5. The first aortic arch is the precursor to all pharyngeal arches Ventral view, human embryonic heart
  • 6. Rostrocaudal maturation of arches Detrait and Etchevers, 2005
  • 7. All pharyngeal arch arteries are never present at once Constant remodeling during embryonic life Growth factor guidance of endothelial cells Immature mural coverage Flow pressures and hemodynamics Obliterated 1st PA Maxillary artery Right dorsal aorta Left dorsal aorta 1st PA 2nd PA 3rd PA 4th PA
  • 8. Craniofacial evolution MOUTH MOUTH r e t i n a s e l e c t i o n o f N C C G n a t h o s t o m e M O U T H p r o s m e s
  • 9. Volumes and surfaces Outer, notched ectoderm Inner, pouched-out endoderm Membranes where they meet Mesodermal core of muscle and vascular endothelium Neural crest mesenchyme hindbrain pros PA1 2 3 4 heart
  • 10. Pouches and grooves 1 2 Persists as tympanic membrane endoderm ectoderm Persists as intratonsillar cleft bpm midbrain 3
  • 11. Endoderm and vascular development Dorsal aorta Arterial vitelline plexus Endoderm 1 st pharyngeal pouch Vitelline arteries Pharyngeal arch arteries Internal carotid Umbilical arteries
  • 12. Endodermal expression of hypoxia-inducible factor 1  HIF1  is a TF activated under hypoxic/growth conditions It effects transcription of pro-vascular factors such as VEGF, ET-1 Etchevers, 2003
  • 13. Endodermal derivatives of pouches Pharyngeal endoderm Derivative 1 Epithelium of tympanic cavity and auditory tube 2 Epithelium of tonsil 3 Inferior parathyroid glands and epithelium of thymus 4 Superior parathyroid glands
  • 14.  
  • 15. Tongue and salivary glands Contributions from most arches Endoderm and mesoderm First oral anterior 2/3 Second Surface contribution not maintained; tonsillar crypts Third pharyngeal posterior 1/3 Fourth Epiglottis and vicinity The salivary glands are ectodermal ingrowths of the oral cavity that associate with NC mesenchyme
  • 16. Structural derivatives Pharyngeal Arch Cranial Nerve Muscle derivative Skeletal Derivative 1 Maxillary Trigeminal nerve (V) Superior oblique Abducens Oculomotor muscles Maxillary, palatine, jugal trabecula cranii 1 Mandibular Trigeminal nerve (V) Muscles of mastication Tensor tympanis Digastric (anterior belly) Incus, ant. lig of malleus palatoquadrate Meckel’s cartilage 2 Hyoid Facial nerve (VII) Muscles of facial expression, digastric (posterior belly), styloid Stapes, hyoid bone Reichert’s cartilage 3 Glossopharyngeal nerve (IX) stylopharyngeas Horns of hyoid Thyroid cartilage 4 and 6 Laryngeal branches of vagus nerve (X) Striated muscles of oesophagus Cricoid cartilage
  • 17. Cartilage derivatives of arches in 24 wk foetus
  • 18. Hox segment identity genes are incompatible with facial skeleton Creuzet et al. (2002) Couly et al. 1993
  • 19. Human embryo aortic arches Courtesy of Next Generation Embryology http://ngembryo.ncl.ac.uk/ngembryo.php
  • 20. Chicken head vessels are in two sectors
  • 21. Vascular derivatives Internal/ external jugular Brachiocephalic Subclavian Sinus venosus? Pharyngeal arch Arteries Veins- tentative 1 st maxillary (shared artery with mandibular) Ophthalmic, ethmoid, ramus superior of stapedial 1 st mandibular Maxillary, mandibular 2 nd hyoid Stapedial 3rd Common and internal carotids 4th Right subclavian (R) Aorta (L) 6th Right proximal pulmonary Left proximal pulmonary Ductus arteriosis
  • 22. The “cardiac” neural crest is a subpopulation of the cephalic crest
  • 23. Heart participation of NCC is necessary but transitory © K Sulik and coll.
  • 24. Oculo-auriculo-vertebral spectrum a.k.a. First arch or Goldenhar syndrome, hemifacial microsomia – though can be bilateral Malformation of jaws, ears and face Experimentally induced by hemorrhage of 2 nd pharyngeal arch Fortuitous genetic mouse model Often overlaps with DiGeorge, VACTERL…
  • 25. Goldenhar, First arch, hemifacial microsomia, oculo-auriculo-vertebral spectrum (MIM 164210) Axial 1-mm 3D FT-CISS MR image through temporal bones. Lemmerling et al., AJNR 2000. Universitätsklinikum Jena semi- circular canals (L) enlarged vestibular aqueduct (R)
  • 27. Congenital vascular anomalies arise from defective arch remodeling Double aortic arch Non-regression of right aortic arch Aberrant right subclavian artery 1% of normal population but 40% of tri 21 or CHD Right aortic arch Retention of the dorsal aorta on right side Ductus arteriosus deflected to right Up to 1/3 of tetralogy of Fallot, 1/10 TGV Interrupted aortic arch Regression of both right and left 4th arch Coarctation of aorta Constriction near normally remodeling ductus arteriosus (6 th arch)
  • 28. Main points Pharyngeal arches are metameric structures They each contain all germ layers, each of which contributes to distinct structures for each arch Hox genes confer identity to differentiate them like for other metameric structures (eg. somites) not with respect to the facial skeleton Arch, facial and heart development are linked