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Increased Netrin downstream of overactive Hedgehog signaling disrupts optic fissure formation

Lusk S, LaPotin S, Presnell JS, Kwan KM
bioRxiv [Preprint]. 2024 Jun 22:2024.06.18.599642. doi: 10.1101/2024.06.18.599642. PMID: 38948711
Uveal coloboma, a developmental eye defect, is caused by failed development of the optic fissure, a ventral structure in the optic stalk and cup where axons exit the eye and vasculature enters. The Hedgehog (Hh) signaling pathway regulates optic fissure development: loss-of-function mutations in the Hh receptor ptch2 produce overactive Hh signaling and can result in coloboma. We previously proposed a model where overactive Hh signaling disrupts optic fissure formation by upregulating transcriptional targets acting both cell- and non-cell-autonomously. Here, we examine the Netrin family of secreted ligands as candidate Hh target genes.
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