Notch signaling can inhibit Xath5 function in the neural plate and developing retina

Molecular and Cellular Neurosciences
Meredith L SchneiderMonica L Vetter

Abstract

Neuronal differentiation is regulated by both positive and negative regulatory factors; however, precisely how these factors interact to regulate retinogenesis is still unclear. We have examined the ability of the Notch pathway to modulate the function of the basic helix-loop-helix factor Xath5. Overexpression of Xath5 by RNA injection into cleavage-stage blastomeres promotes ectopic neurogenesis at neural plate stages and ganglion cell differentiation in the developing retina. We found that these activities of Xath5 could be inhibited by coexpression of activated Notch. Notch inhibition of Xath5 function was reversed by coexpression with the zinc finger protein X-MyT1. The Notch effector enhancer-of-split related 1 (ESR1) also blocked Xath5 activity but efficient inhibition by ESR1 required the DNA binding basic domain and the conserved WRPW motif. In addition, ESR1 inhibited the ability of Xath5 to directly activate the expression of XBrn3d, a transcription factor involved in retinal ganglion cell development. Xath5 could upregulate expression of X-Delta-1, ESR1, and ESR3, suggesting that Xath5 participates in a regulatory loop with the Notch pathway.

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Citations

May 8, 2008·Proceedings of the National Academy of Sciences of the United States of America·Xiuqian MuWilliam H Klein
Dec 1, 2005·Development, Growth & Differentiation·Yanzhen Cui
Oct 16, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Amy N RiesenbergNadean L Brown
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Mar 31, 2021·Cellular and Molecular Life Sciences : CMLS·Jianyi Lyu, Xiuqian Mu
Aug 5, 2005·Development·Lidia Matter-SadzinskiJean-Marc Matter
Feb 1, 2003·Mechanisms of Development·Nicolas NègreAnne Marie Martinez
Aug 2, 2003·Progress in Retinal and Eye Research·Till Marquardt
Mar 24, 2004·Seminars in Cell & Developmental Biology·Xiuqian Mu, William H Klein

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