Holoprosencephaly is associated with defects in signaling of which developmental pathway?

Holoprosencephaly is associated with defects in signaling of which developmental pathway?

• A. WNT
• B. NOTCH
• C. SHH
• D. FGF

Answer: (C)

Sonic Hedgehog signaling is the key driver of ventral forebrain patterning and midline separation during early brain development. SHH acts as a critical morphogen, creating a gradient that instructs neural progenitors to adopt proper ventral identities and drives the splitting of the forebrain vesicle into two hemispheres. When SHH signaling is disrupted, the forebrain fails to divide correctly, producing holoprosencephaly along a spectrum from severe (alobar) to milder (lobar) forms, often with facial midline defects like cyclopia in the most severe cases. Other pathways like WNT, NOTCH, and FGF play important roles in various aspects of CNS development, but holoprosencephaly is most strongly linked to defects in SHH signaling.

Sonic Hedgehog signaling is the key driver of ventral forebrain patterning and midline separation during early brain development. SHH acts as a critical morphogen, creating a gradient that instructs neural progenitors to adopt proper ventral identities and drives the splitting of the forebrain vesicle into two hemispheres. When SHH signaling is disrupted, the forebrain fails to divide correctly, producing holoprosencephaly along a spectrum from severe (alobar) to milder (lobar) forms, often with facial midline defects like cyclopia in the most severe cases. Other pathways like WNT, NOTCH, and FGF play important roles in various aspects of CNS development, but holoprosencephaly is most strongly linked to defects in SHH signaling.