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Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
Maxillofacial Embryology And Development
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Maxillofacial Embryology And Development

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Course in facial development for European Course in Neuroradiology in Tarragona, Spain, on 12 octobre 2008. For questions, e-mail to etchevers at free dot fr. Download to play the animations …

Course in facial development for European Course in Neuroradiology in Tarragona, Spain, on 12 octobre 2008. For questions, e-mail to etchevers at free dot fr. Download to play the animations (especially as some pictures are covered by others)

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  • 1. Maxillofacial embryology and development Heather Etchevers, Ph.D. INSERM
  • 2. Defining some terms for orientation <ul><li>“ Germ layers” </li></ul><ul><ul><li>Ectoderm </li></ul></ul><ul><ul><li>Mesoderm </li></ul></ul><ul><ul><li>Endoderm </li></ul></ul><ul><ul><li>(Neural crest) </li></ul></ul><ul><li>Four dimensions </li></ul><ul><ul><li>Dorsoventral </li></ul></ul><ul><ul><li>Rostrocaudal </li></ul></ul><ul><ul><li>Mediolateral </li></ul></ul><ul><ul><li>Time!! </li></ul></ul>Scanning EM Human embryo, 24 d All EM photos © K Sulik and M Vekemans Photo © A Thornton
  • 3. Embryonic constituents
  • 4. The five “fingers” of the face <ul><li>Medial </li></ul><ul><ul><li>Frontonasal bud </li></ul></ul><ul><ul><ul><li>Medial </li></ul></ul></ul><ul><ul><ul><li>Lateral </li></ul></ul></ul><ul><li>Bilaterally paired </li></ul><ul><ul><li>First pharyngeal arch </li></ul></ul><ul><ul><ul><li>Maxillary </li></ul></ul></ul><ul><ul><ul><li>Mandibular </li></ul></ul></ul><ul><ul><li>Second pharyngeal arch </li></ul></ul><ul><ul><ul><li>Hyoid </li></ul></ul></ul><ul><ul><li>Second and beyond will be part of neck </li></ul></ul>human embryo, 28 days eye
  • 5. In the second month… eye
  • 6. Growth of segments <ul><li>Normal development = differential growth </li></ul><ul><li>Controlled by cell behaviour </li></ul><ul><ul><li>programmed death </li></ul></ul><ul><ul><li>migration </li></ul></ul><ul><ul><li>differentiation </li></ul></ul>
  • 7. Skull components from facial buds Couly et al. (1993) Development 117:409
  • 8. Rostrocaudal axis recapitulates temporal maturation 24 days future face and head
  • 9. embryo Endoderm
  • 10. The pharyngeal arches <ul><li>Metameric </li></ul><ul><ul><li>5 in mammals </li></ul></ul><ul><ul><li>Numbered historically 1-4, 6 </li></ul></ul><ul><li>Epithelia </li></ul><ul><ul><li>Outer, lateral ectodermal bulges </li></ul></ul><ul><ul><li>Inner, medial endodermal pouches </li></ul></ul><ul><ul><li>Meet as membranous grooves </li></ul></ul><ul><li>Mesenchyme </li></ul><ul><ul><li>Mesodermal core (artery and muscle) </li></ul></ul><ul><ul><li>Neural crest cells (everything else) </li></ul></ul>
  • 11.  
  • 12. Cephalic neural crest mesectodermal derivatives Support tissues for pituitary , salivary and lachrymal glands Tendons for cephalic muscles dermis adipose tissue cartilage bone periost dura mater pia mater pericytes brain epidermis
  • 13. Neural crest cells fill out the pharyngeal arches
  • 14. Fate-mapping with chick-quail chimeras Couly and Le Douarin
  • 15. Segmental distribution of progeny in some disease Poulet E8 Etchevers et al. (2001) Sturge-Weber syndrome
  • 16. Regulation of cell behavior by diffusible signals <ul><li>Initiators of protein signalling cascades </li></ul><ul><ul><li>Membrane </li></ul></ul><ul><ul><li>Cytoplasmic second messengers </li></ul></ul><ul><ul><li>Transcription factor activation or repression </li></ul></ul><ul><ul><li>Target transcription or inactivation </li></ul></ul><ul><li>Physiological role for known oncogenic pathways </li></ul><ul><ul><li>FGF, Wnt, Notch/Delta, EGF, Shh… </li></ul></ul>
  • 17. Congenital craniofacial malformations <ul><li>Over 700 of the approx 5,000 known inherited conditions affect the craniofacial area </li></ul><ul><li>Many of these perturb signals directing neural crest </li></ul><ul><ul><li>Migration </li></ul></ul><ul><ul><li>Proliferation or programmed cell death </li></ul></ul><ul><ul><li>Differentiation </li></ul></ul>
  • 18. Cleft lip/palate <ul><li>Physiological cleft lip until 6-7 weeks </li></ul><ul><li>Cleft lip/palate </li></ul><ul><ul><li>Approx 1 per 800-1,000 births </li></ul></ul><ul><ul><li>Genetic component </li></ul></ul><ul><ul><ul><li>More frequent in some populations </li></ul></ul></ul><ul><ul><ul><li>More frequent in males </li></ul></ul></ul><ul><ul><ul><li>20% associated with ~100 genetic syndromes </li></ul></ul></ul><ul><li>Physiological cleft palate until 10 weeks </li></ul><ul><ul><li>Isolated = approx 1 per 2,000 births </li></ul></ul><ul><ul><li>50% syndromic </li></ul></ul><ul><ul><li>No racial predominance but females > males </li></ul></ul>
  • 19. Clefts at 7 weeks’ development eye
  • 20. Facial clefting Wilkie and Morris-Kay, 2001 Maxillary bud derivatives
  • 21. DiGeorge syndrome <ul><li>More frequent cleft lip/palate </li></ul><ul><li>Small jaw </li></ul><ul><li>Small upper lip/mouth </li></ul><ul><li>Eyes slanted upward or downward </li></ul><ul><li>Low-set and/or abnormal folding of ears </li></ul><ul><li>Short stature, mild to moderate learning difficulties </li></ul><ul><li>Underdeveloped parathyroid and thymus </li></ul><ul><li>Cardiac malformations </li></ul>Digilio et al., 2005
  • 22. Del22q11.2 – often but not always TBX1 from S. Lyonnet Aided and abetted by a polymorphism 1Kb upstream of VEGF ! Stalmans et al., 2003
  • 23. Tbx1 knockout mouse phenocopies DGS patients Jerome and Papaioannou, 2001
  • 24. The holoprosencephaly spectrum Wilkie and Morris-Kay, 2001; image from Muenke, M. & Beachy, P. A. in The Metabolic and Molecular Bases of Inherited Disease 8th edn (eds Scriver, C. R. et al .) 6203–6230 (McGraw–Hill, New York, 2001). proboscis Single median incisor No philtrum
  • 25. Cell signaling via hedgehog family after van Tuyl et Post., 2002 Patched Sonic/Indian hedgehog Gli and Zic TF genes cyclopamine
  • 26. Neural crest ablation can phenocopy lack of Shh Normal 8d chicken embryo Neural crest-ablated chicken embryos
  • 27. Shh and Wnt signals needed for growth of maxillofacial crest bones Jeong et al., 2004 Wt no ß-catenin in NCC Brault et al. 2001
  • 28. Key points <ul><li>The pharyngeal arches are metameric structures containing tissues from all germ layers </li></ul><ul><li>The upper lip and palate are subject to clefts because of facial fusion of frontonasal and maxillary tissues during development </li></ul><ul><li>Multipotent neural crest mesenchyme is a major structural component of the face </li></ul>
  • 29. Save the trees! Save your memory! I will make this Powerpoint presentation available and downloadable as of next week on SlideShare. http://www.slideshare.net/Alethea Please comply with fair use (cf Wikipedia if you need to) as the images and photographs are copyrighted by their authors. I will correct any lacunae in attributions if you leave a comment.

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