Disrupting Hedgehog signaling in melanocytes by SUFU knockout leads to ocular melanocytosis and anterior segment malformation

Abstract

Hedgehog (Hh) signaling is well known for its crucial role during development but its specific role in individual cell lineages is less well characterized. Here we disrupted Hh signaling specifically in melanocytes by using a Cre-mediated cell type-specific knockout strategy of the Hh regulator Suppressor of Fused (Sufu). Interestingly, corresponding mice are fully pigmented and show no developmental alterations in melanocyte numbers or distribution in skin and hair follicles. However, there are ectopic melanoblasts visible in the anterior chamber of the eye that are eventually displays a severe malformation. Choroidal melanocytes remain unaltered. Surprisingly, the abnormal accumulation of anterior uveal melanoblasts is not the result of increased cell proliferation but of increased migration to ectopic locations such as the cornea. In melanoblasts in vitro, Sufu knockdown replicates the increase in cell migration without affecting proliferation and is mediated by an increased level of phospho-ERK brought about by a reduction of the levels of the repressor form of GLI3. The results highlight the developmental divergence of distinct melanocyte subpopulations and may shed light on the pathogenesis of human ocular melanocytosis.

First person – Weizhuo Wang

“… ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping researchers promote themselves alongside their papers. Weizhuo Wang is first author on ‘ Disrupting Hedgehog signaling in melanocytes by SUFU knockout leads to ocular melanocytosis and anterior segment malformation ', published in DMM. Weizhuo is a PhD student in the lab of Ling Hou at Wenzhou Medical University, Wenzhou, China, investigating ocular pigment cell biology and associated disease.…”