Practice question

Evidence for Shh involvement in eye field separation came from loss-of-function genetics. Chiang and colleagues generated Shh null mice by targeted disruption and observed single forebrain vesicle, absence of ventral diencephalon and fusion of optic primordia into single cyclopic eye located ventrally. Molecular analysis revealed ectopic expansion of Pax6 and loss of Pax2 across midline, confirming Shh normally represses Pax6 medially. This phenotype recapitulated human holoprosencephaly associated with SHH mutations, establishing experimental proof that midline-derived Shh signal bisects single eye field into bilateral domains essential for two eyes and nose formation.