Developmental vascular regression is regulated by a Wnt/β-catenin, MYC and CDKN1A pathway that controls cell proliferation and cell death

Development
Gowri NayakRichard A Lang

Abstract

Normal development requires tight regulation of cell proliferation and cell death. Here, we have investigated these control mechanisms in the hyaloid vessels, a temporary vascular network in the mammalian eye that requires a Wnt/β-catenin response for scheduled regression. We investigated whether the hyaloid Wnt response was linked to the oncogene Myc, and the cyclin-dependent kinase inhibitor CDKN1A (P21), both established regulators of cell cycle progression and cell death. Our analysis showed that the Wnt pathway co-receptors LRP5 and LRP6 have overlapping activities that mediate the Wnt/β-catenin signaling in hyaloid vascular endothelial cells (VECs). We also showed that both Myc and Cdkn1a are downstream of the Wnt response and are required for hyaloid regression but for different reasons. Conditional deletion of Myc in VECs suppressed both proliferation and cell death. By contrast, conditional deletion of Cdkn1a resulted in VEC overproliferation that countered the effects of cell death on regression. When combined with analysis of MYC and CDKN1A protein levels, this analysis suggests that a Wnt/β-catenin and MYC-CDKN1A pathway regulates scheduled hyaloid vessel regression.

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Citations

Jun 24, 2020·Disease Models & Mechanisms·Olga Medina-MartinezMilan Jamrich
Jun 17, 2020·Investigative Ophthalmology & Visual Science·Kamesh DhamodaranVijayKrishna Raghunathan
Oct 7, 2020·Proceedings of the National Academy of Sciences of the United States of America·Christopher M SchaferCourtney T Griffin
Jun 27, 2021·Nature Communications·Jedrzej HoffmannStefanie Dimmeler

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