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C. elegans EVI1 proto-oncogene, EGL-43, is necessary for Notch-mediated cell fate specification and regulates cell invasion

Hwang, Byung Joon and Meruelo, Alejandro D. and Sternberg, Paul W. (2007) C. elegans EVI1 proto-oncogene, EGL-43, is necessary for Notch-mediated cell fate specification and regulates cell invasion. Development, 134 (4). pp. 669-679. ISSN 0950-1991. https://resolver.caltech.edu/CaltechAUTHORS:HWAdev07

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Abstract

During C. elegans development, LIN-12 (Notch) signaling specifies the anchor cell (AC) and ventral uterine precursor cell (VU) fates from two equivalent pre-AC/pre-VU cells in the hermaphrodite gonad. Once specified, the AC induces patterned proliferation of vulva via expression of LIN-3 (EGF) and then invades into the vulval epithelium. Although these cellular processes are essential for the proper organogenesis of vulva and appear to be temporally regulated, the mechanisms that coordinate the processes are not well understood. We computationally identified egl-43 as a gene likely to be expressed in the pre-AC/pre-VU cells and the AC, based on the presence of an enhancer element similar to the one that transcribes lin-3 in the same cells. Genetic epistasis analyses reveal that egl-43 acts downstream of or parallel to lin-12 in AC/VU cell fate specification at an early developmental stage, and functions downstream of fos-1 as well as upstream of zmp-1 and him-4 to regulate AC invasion at a later developmental stage. Characterization of the egl-43 regulatory region suggests that EGL-43 is a direct target of LIN-12 and HLH-2 (E12/47), which is required for the specification of the VU fate during AC/VU specification. EGL-43 also regulates basement membrane breakdown during AC invasion through a FOS-1-responsive regulatory element that drives EGL-43 expression in the AC and VU cells at the later stage. Thus, egl-43 integrates temporally distinct upstream regulatory events and helps program cell fate specification and cell invasion.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1242/dev.02769DOIUNSPECIFIED
http://dev.biologists.org/cgi/content/abstract/134/4/669PublisherUNSPECIFIED
ORCID:
AuthorORCID
Sternberg, Paul W.0000-0002-7699-0173
Additional Information:Published by The Company of Biologists 2007. Accepted 30 November 2006. First published online 10 January 2007. We thank C. Van Buskirk, G.B. Choi, J. Fernandes, E. Hallem, M. Kato, C. Robinson, and G. Schindelman for carefully reading the manuscript; J. DeModena for Ab staining; S. Gharib for help with the RNAi screen; S. Mitani at Tokyo Women's Medical University for the egl-43(tm1802) strain; J. Kimble at the University of Wisconsin-Madison and Michael Krause at NIH for LAG-3 (SEL-8) and HLH-2 antibodies; M. H. Lee at the University of Wisconsin-Madison for helping with the ChIP assay; and B. Gupta, H.-M. Muller, A. Saldanha, E. Schwarz, and L. Warren for discussions about ClusterSearch. P.W.S. is an investigator of the Howard Hughes Medical Institute. B.J.H. is supported by a NHGRI/NIH Genome Scholar Development and Faculty Transition Award (K22HG02907-02). The development of ClusterSearch was supported in part by the Caltech/SURF award from Dr Ashley to A.D.M. Supplementary material for this article is available at http://dev.biologists.org/cgi/content/full/134/4/669.
Funders:
Funding AgencyGrant Number
Howard Hughes Medical InstituteUNSPECIFIED
National Institutes of HealthK22HG02907-02
Summer Ungraduate Research Fund (SURF), CaltechUNSPECIFIED
Subject Keywords:EGL-43, HLH-2, FOS-1, LIN-12/Notch, Cell fate specification, Cell invasion
Issue or Number:4
Record Number:CaltechAUTHORS:HWAdev07
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:HWAdev07
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:11719
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:21 Sep 2008 06:59
Last Modified:03 Mar 2020 13:01

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