RRC ID 3588
Author Hwang BJ, Meruelo AD, Sternberg PW.
Title C. elegans EVI1 proto-oncogene, EGL-43, is necessary for Notch-mediated cell fate specification and regulates cell invasion.
Journal Development
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.
Volume 134(4)
Pages 669-79
Published 2007-2
DOI 10.1242/dev.02769
PII dev.02769
PMID 17215301
MeSH Animals Basic Helix-Loop-Helix Transcription Factors Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins / physiology* Cell Movement / physiology* Computational Biology Disorders of Sex Development Embryonic Induction* Epidermal Growth Factor Epistasis, Genetic Gonads / growth & development Membrane Proteins / physiology* Organogenesis Receptors, Notch / physiology Stem Cells / cytology* Transcription Factors / physiology*
IF 5.413
Times Cited 28
C.elegans tm1802