A newborn has microcephaly, a single midline eye, and absent nasal structures. Cytogenetic analysis shows trisomy 13. The malformation results from failure of cleavage of the forebrain into two cerebral hemispheres. Which signalling pathway, acting at the prechordal plate, is implicated?
- A Fibroblast growth factor 8 gradient
- B Wnt-beta-catenin signalling
- C Sonic hedgehog signalling ✓
- D Bone morphogenetic protein antagonism by noggin
Correct answer: C. Sonic hedgehog signalling
Explanation
Holoprosencephaly results from failed division of the prosencephalon into two hemispheres. Sonic hedgehog signalling from the prechordal plate is required for midline facial and forebrain patterning, and loss of this signal produces the classic combination of cyclopia, absent midline facial structures, and a single ventricle. It is strongly associated with trisomy 13 and maternal diabetes. BMP antagonism by noggin relates to neural induction, and FGF8 acts later at the isthmic organiser and apical ectodermal ridge.
Reference: Langman's Medical Embryology, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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