Maxillofacial Embryology And Development
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Transcript of Maxillofacial Embryology And Development
Maxillofacial embryology and development
Heather Etchevers, Ph.D.
INSERM
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Defining some terms for orientation
“Germ layers” Ectoderm Mesoderm Endoderm (Neural crest)
Four dimensions Dorsoventral Rostrocaudal Mediolateral Time!!
Scanning EMHuman embryo, 24 dAll EM photos ©K Sulik and M Vekemans
Photo © A Thornton
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Embryonic constituents
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
The five “fingers” of the face Medial
Frontonasal bud Medial Lateral
Bilaterally paired First pharyngeal arch
Maxillary Mandibular
Second pharyngeal arch Hyoid
Second and beyond will be part of neck
eye
human embryo, 28 days
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
In the second month…
eye
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Growth of segments
Normal development = differential growth Controlled by cell behaviour
programmed death migration differentiation
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Skull components from facial buds
Couly et al. (1993) Development 117:409
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Rostrocaudal axis recapitulates temporal maturation
24 days
future face and head
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
embryo
Endoderm
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
The pharyngeal arches
Metameric 5 in mammals Numbered historically 1-4, 6
Epithelia Outer, lateral ectodermal bulges Inner, medial endodermal pouches Meet as membranous grooves
Mesenchyme Mesodermal core (artery and muscle) Neural crest cells (everything else)
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Cephalic neural crest mesectodermal derivatives
Support tissues for pituitary, salivary and lachrymal glandsTendons for cephalic muscles
dermisadipose tissuecartilageboneperiostdura materpia materpericytes brain
epidermis
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Neural crest cells fill out the facial buds
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Fate-mapping with chick-quail chimeras
Couly and Le Douarin
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Poulet E8
r6r5r4
r3r2r1
PD,AM,PM
Sturge-Weber syndrome
Segmental distribution of progeny in some disease
Etchevers et al. (2001)
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Regulation of cell behavior by diffusible signals
Initiators of protein signalling cascades Membrane Cytoplasmic second messengers Transcription factor activation or repression Target transcription or inactivation
Physiological role for known oncogenic pathways FGF, Wnt, Notch/Delta, EGF, Shh…
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Congenital craniofacial malformations
Over 700 of the approx 5,000 known inherited conditions affect the craniofacial area
1/3 of birth defects have CF malformations Many of these perturb signals directing neural
crest Migration Proliferation or programmed cell death Differentiation
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Cleft lip/palate Physiological cleft lip until 6-7 weeks Approx 1 per 800-1,000 births Genetic component to cleft lip ± palate
More frequent in some populations More frequent in males 20% associated with ~100 genetic syndromes
Physiological cleft palate until 10 weeks No racial predominance but females > males Isolated = approx 1 per 2,000 births 50% syndromic
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Clefts at 7 weeks’ development
eye
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Facial clefting
Wilkie and Morris-Kay, 2001
Maxillary budderivatives
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
DiGeorge syndrome
More frequent cleft lip/palate Small jaw Small upper lip/mouth Eyes slanted upward or downward Low-set and/or abnormal folding of ears Short stature, mild to moderate learning
difficulties Underdeveloped parathyroid and thymus Cardiac malformations
Digilio et al., 2005
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Tbx1 knockout mouse phenocopies DGS patients
Jerome and Papaioannou, 2001
Bindingsite
Target gene
Transcriptionfactor
RNA, then protein
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
from S. Lyonnet
Del22q11.2 – often but not always TBX1 itself: distant regulation
Aided and abetted by a polymorphism 1Kb upstream of VEGF !Stalmans et al., 2003
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
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 incisorNo philtrum
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Cell signaling via hedgehog family
after van Tuyl et Post., 2002
Patched
Sonic/Indian hedgehog
Gli and Zic TF genes
cyclopamine
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Neural crest ablation can phenocopy lack of Shh
Normal 8d chicken embryo Neural crest-ablated chicken embryos
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
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
WN
TsINV
DVL
SCRIB
DAAM
RHOA
JNK
FYIN
ROCK
SHH
PTCH
Cytoskeletal changes Transcriptional changes
PTK7
actins
BBS
CELSR
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
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/ddq030After Wilder
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
Key points
The pharyngeal arches are metameric structures containing tissues from all germ layers
The upper lip and palate are subject to clefts because of facial fusion of frontonasal and maxillary tissues during development
Multipotent neural crest mesenchyme is a major structural component of the face
Facialmodules
Developmentover time
Neural crestcontributions
Facialmalformations Summary
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.