SHH and coloboma: Notably, RA is also a key regulator of ocular fissure closure, as both increased and decreased RA result in colobomas in mice and zebrafish.58, , –61 Exposure to exogenous RA inhibits Shh expression in the midline floor plate.62 We observed that the overexpression of cyp1b1 not only increased RA levels throughout the developing head and eye, but also increased shha expression.