Craniofacial Embryology

• How can developmental processes lead to cancers?

  Developmental genes can be reactivated inappropriately and uncontrolled.
• What is the role of transcription factors in congenital heart disease?

  They control the expression of genes to build tissues and organs.
• What happens during segmentation and patterning in development?

  Different body segments have different fates, such as in the spinal cord and pharyngeal arches.
• What is the significance of the neural crest in cranial development?

  Neural crest cells give rise to the PNS and musculoskeletal tissues.
• What is epithelial to mesenchymal transition (EMT) in neural crest cells?

  It is the process by which neural crest cells migrate and differentiate into various tissues.
• What does ectomesenchyme give rise to?

  It gives rise to cartilage and bone.
• How do cranial neural crest and placodes contribute to morphogenesis?

  They undergo cell migration and shape change to create the pharyngeal arches and facial morphology.
• What are the derivatives of each pharyngeal arch?

  Each arch has specific neural, muscular, and skeletal derivatives.
• What are endodermal pharyngeal pouches?

  They are outpockets formed by the endoderm lining of the pharynx between pharyngeal arches.
• How does Shh signaling affect cranial development?

  Shh signaling is crucial for cell proliferation and development of facial prominences.
• What happens when Shh signaling is disrupted?

  Disruption can lead to conditions like cleft palate and holoprosencephaly.
• What is the relationship between Shh mutations and holoprosencephaly?

  About 25% of mutations in holoprosencephaly are in the Shh gene itself.
• How do signaling pathways relate to cancer development?

  Signaling pathways like FGF, Wnt, and Shh regulate cell division and can lead to cancer if disrupted.
• What is the primary oncogenic driver in thyroid cancer?

  RTK signaling is the main driver of tumorigenesis in thyroid cancer.
• Which pathways are implicated in colorectal cancer?

  Wnt, RTK, and TGFβ pathways are all implicated in colorectal cancer.
• What are the key signaling pathways involved in cranial morphogenesis?

  • Shh (Sonic Hedgehog)
  • Wnt
  • BMP/TGF-β
  • FGF
• What are the common congenital craniofacial defects?

  • Cleft palate
  • Holoprosencephaly
  • Frontonasal dysplasia
• Sense organs in the head develop from a series of specialised thickening of ectoderm (placodes) -> often capable of differentiating into neurons
• What occurs in neurulation?

  Formation of the neural tube

  A) 18

  B) 20

  C) 22

  D) 23

  E) amnion

  F) Neural fold

  G) Neural plate

  H) Neural groove

  I) Somite

  J) Primitive node

  K) Primitive streak

  L) Neural fold

  M) Pericardial bulge

  N) Somite

  O) Anterior neuroport

  P) Posterior neuropore

  
• What is the neural crest?

  Multipotent population of neuroectodermal cells

  Migrate from dorsal neural tube

  Neural crest cells are progenitor cells that migrate out of the CNS & give rise to PNS & other tissues
• In the head, the neural crest also forms MSK tissues.
• Neural crest cells undergo EMT & migrate laterally and ventrally throughout the primary body axis.
• Cranial neural crest can give rise to ectomesenchyme (cartilage & bone).

  Vagal, trunk & sacral neural crest do not
• Morphogenesis (cranial) - ADD MORE

  Combined actions of cranial neural crest & placodes undergo extensive cell migration & tissue shape change -> creating pharyngeal arches -> creation of morphology of the human face
• Why are there strange patterns of innervation of the face (e.g. tongue innervation)?

  Innervation of pharyngeal arches (by cranial nerves) occurs before morphogenesis -> innervation is 'carried' with the arches as they develop into facial structures -> strange patterns of innervation of the face
• What is Wnt/PCP signalling involved in>

  Orientating cell & tissue growth

  Controls cell migration

  Oncogenesis & metastasis
• Foetal alcohol syndrome is heavily associated with vulnerable groups.
• What is the effect of alcohol on embryology?

  Decreases Shh signalling -> affects neural crest migration & facial morphogenesis

  Variation in Shh signalling levels determines the extent of symptom presentation between holoprosencephaly & frontonasal dysplasia