Open AccessDevelopmental vascular regression is regulated by a Wnt/β-catenin, MYC, P21 (CDKN1A) pathway that controls cell proliferation and cell death
Author(s) -
Gowri Nayak,
Yoshinobu Odaka,
Vikram Prasad,
Alyssa Solano,
EuiJu Yeo,
Shruti Vemaraju,
Jeffery D. Molkentin,
Andreas Trumpp,
Bart O. Williams,
Sujata Rao,
Richard A. Lang
Publication year - 2018
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.154898
Subject(s) - biology , wnt signaling pathway , cell growth , beta catenin , catenin , cancer research , microbiology and biotechnology , cell cycle , cell , regression , programmed cell death , medicine , signal transduction , genetics , apoptosis , psychology , psychoanalysis
Normal development requires tight regulation of cell proliferation and cell death. Here, we 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 P21 (CDKN1A), both established regulators of cell cycle progression and cell death. Our analysis showed that the Wnt pathway coreceptors LRP5 and LRP6 have overlapping activities mediating 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 over-proliferation that countered the effects of cell death on regression. When combined with analysis of MYC, and P21 protein levels, this analysis suggests that a Wnt/β-catenin, MYC-P21 pathway regulates scheduled hyaloid vessel regression.