A newborn has microcephaly, a single midline eye with a proboscis above it, and congenital heart disease. MRI shows fusion of the cerebral hemispheres with a single ventricle. Which signalling pathway failed during development?

• A Bone morphogenetic protein mediated dorsal neural tube patterning
• B Sonic hedgehog mediated cleavage of the prosencephalon ✓
• C Retinoic acid mediated hindbrain segmentation
• D Wnt mediated dorsal-ventral spinal cord patterning

Explanation

Holoprosencephaly is failure of cleavage of the prosencephalon into two cerebral hemispheres, associated with midline facial defects ranging from cyclopia to hypotelorism. Sonic hedgehog signalling from the prechordal plate and ventral forebrain drives this midline separation, so loss of SHH activity (as in trisomy 13, or mutations affecting SHH) produces the defect. BMP and Wnt pattern the dorsal neural tube and are unrelated to forebrain cleavage.

Reference: Langman's Medical Embryology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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