Affiliation:
1. Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA
2. Science and Technology Research Program, Smithtown High School East, St. James, NY 11780-1833, USA
Abstract
Cellular invasion is a key part of development, immunity, and disease. Using the in vivo model of C. elegans anchor cell invasion, we characterize the gene regulatory network that promotes cell invasion. The anchor cell is initially specified in a stochastic cell fate decision mediated by Notch signaling. Previous research has identified four conserved transcription factors, fos-1a (Fos), egl-43 (EVI1/MEL), hlh-2 (E/Daughterless) and nhr-67 (NR2E1/TLX), that mediate anchor cell specification and/or invasive behavior. Connections between these transcription factors and the underlying cell biology that they regulate are poorly understood. Here, using genome editing and RNA interference, we examine transcription factor interactions before and after anchor cell specification. Initially, these transcription factors function independently of one another to regulate LIN-12 (Notch) activity. Following anchor cell specification, egl-43, hlh-2, and nhr-67, function largely parallel to fos-1 in a type I coherent feed-forward loop with positive feedback to promote invasion. Together, these results demonstrate that the same transcription factors can function in cell fate specification and differentiated cell behavior, and that a gene regulatory network can be rapidly assembled to reinforce a post-mitotic, pro-invasive state.
Funder
National Institutes of Health
Damon Runyon Cancer Research Foundation
American Cancer Society
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Cited by
29 articles.
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