Hedgehog-dependent E3-ligase Midline1 regulates ubiquitin-mediated proteasomal degradation of Pax6 during visual system development

The first morphological sign of vertebrate eye formation is the appearance of eye vesicles on both sides of the ventral diencephalon, which primarily originate from a uniform Pax6-positive eye field. A key regulator for this process, which coincides with the establishment of the proximo-distal axis of the eye with eyestalk and retina, is the morphogen Shh. Shh induces the expression of pax2, which represses pax6 in the presumptive eyestalk region. Here, we report on the identification of the E3-ligase Mid1, which is induced by Shh and targets transcription factor Pax6 for proteasomal degradation. Our findings might provide insight into a mechanism, in which a morphogen initiates the degradation of a transcription factor to form sharp boundaries of gene expression.