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)

1. Maxillofacial embryology and development Heather Etchevers, Ph.D. INSERM

3. Embryonic constituents

5. In the second month… eye

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

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 facial buds

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

19. Clefts at 7 weeks’ development eye

20. Facial clefting Wilkie and Morris-Kay, 2001 Maxillary bud derivatives

22. Tbx1 knockout mouse phenocopies DGS patients Jerome and Papaioannou, 2001 Binding site Target gene RNA, then protein Transcription factor

23. Del22q11.2 – often but not always TBX1 itself: distant regulation from S. Lyonnet Aided and abetted by a polymorphism 1Kb upstream of VEGF ! Stalmans et al., 2003

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. Primary cilia transduce Sonic hedgehog signaling Rohatgi, R., Milenkovic, L. and Scott, M.P. (2007). Science, 317, 372–376. Photo from PKD group, Mayo Clinic; figure adapted from Kibar et al., Clin Genet 2007 Cilium PK VANGL FZ WNTs INV DVL SCRIB DAAM RHOA JNK FY IN ROCK SHH PTCH Cytoskeletal changes Transcriptional changes PTK7 actins BBS CELSR

28. Midline facial disorders arise from defects in primary cilia Figure 9 from Brugmann et al., Human Molecular Genetics 2010, Vol. 19, No. 8 1577–1592 doi:10.1093/hmg/ddq030 After Wilder

30. I will make this Powerpoint presentation available and downloadable as of next week on SlideShare, but you also have it available as part of this course. 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.