Roles of sonic hedgehog signaling in retinal patterning and neurogenesis during mammalian eye development

The sonic hedgehog (Shh) signaling pathway is essential for the patterning, growth and morphogenesis of many tissues. During early eye development, Shh is required for the formation of the two optic vesicles, which give rise to the retina, retinal pigment epithelium and optic stalk. It also regulates the balance between proliferation and differentiation during retinal histogenesis, a key process shaping the cellular architecture of the mature retina. Despite these roles, the temporal dynamics, regional functions and downstream consequences of Shh signaling during retinal development remain incompletely understood. Here, we performed a comprehensive analysis of Shh pathway function across retinal development in mice using temporally and spatially controlled deletion of smoothened (Smo), an essential pathway transducer. This strategy revealed context-dependent requirements for Shh signaling in eye patterning. In addition, we find that Shh signaling coordinates retinal neurogenesis by maintaining the progenitor pool while regulating progenitor competence, ensuring appropriate proportions of retinal cell types. Together, our findings identify new links between Shh signaling, regional patterning and the temporal control of neurogenesis during mammalian retinal development.