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#cyclopia

2 public questions tagged with this topic.

Eye Lens Induction -ll

Which signaling pathway mutation most commonly leads to cyclopia and midline structure defects?

Mutations disrupting Sonic hedgehog signaling cause cyclopia and holoprosencephaly due to failure of midline patterning. SHH secreted from prechordal plate and notochord suppresses Pax6 centrally and splits single eye field into bilateral domains. Loss of SHH leaves Pax6 expressed across midline, fusing optic vesicles into single central eye and causing midline structure defects including forebrain, nose, and palate. Wingless, Notch, and EGF pathways regulate other embryonic processes but not midline separation, making SHH pathway most common cause of cyclopia documented in humans.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 12: Eye development – SHH midline patterning and cyclopia.

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Teratogens

Teratogen causing cyclopia in embryos:

Cyclopia single median eye results from failure of embryonic forebrain to divide into bilateral hemispheres due to deficient midline specification by Sonic hedgehog pathway. Steroidal alkaloid cyclopamine from Veratrum californicum binds Smoothened G-protein coupled receptor blocking hedgehog signal transduction, preventing expression of Pax2 and separation of eye field into two optic vesicles. Lambs whose mothers grazed plant and chick embryos treated experimentally display holoprosencephaly with cyclopia. Classic teratological outbreak traced to cyclopamine led to discovery of hedgehog pathway requirement. Thus teratogen causing cyclopia is cyclopamine potent sonic hedgehog antagonist producing midline facial defect.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: Cyclopamine causes cyclopia Shh inhibition.

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