Editor's Evaluation: Lhx2 Is a Progenitor-Intrinsic Modulator of Sonic Hedgehog Signaling During Early Retinal Neurogenesis

The study investigated the role of the transcription factor Lhx2 in modulating the Sonic Hedgehog (Shh) signaling pathway during early retinal neurogenesis in mice. Lhx2 was found to be a crucial multilevel regulator of Shh signaling, promoting the expression of pathway genes necessary for effective activation and maintenance of signaling in retinal progenitor cells (RPCs). It up-regulated Shh co-receptors Cdon and Gas1, essential for signaling competence, and linked the Shh pathway to downstream targets, enhancing RPCs' ability to respond to Shh signaling. Despite Lhx2-deficient RPCs showing an attenuated response, the Shh pathway downstream of Patched and Smoothened remained functional. The study highlighted Lhx2's role in integrating Shh signaling into the retinal neurogenesis program, crucial for retinal development.