A developmental gene regulatory network for invasive differentiation of the C. elegans anchor cell

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 invasive differentiation. 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 differentiation. Connections between these transcription factors and the underlying cell biology that they regulate is poorly understood. Here, using genome editing and RNA interference, we examine transcription factor interactions prior to and after anchor cell specification. During invasion we identify that egl-43, hlh-2, and nhr-67 function together in a type I coherent feed-forward loop with positive feedback. Conversely, prior to specification, these transcription factors function independent of one another to regulate LIN-12 (Notch) activity. Together, these results demonstrate that, although the same transcription factors can function in fate specification and differentiated cell behavior, a gene regulatory network can be rapidly re-wired to reinforce a post-mitotic, pro-invasive state.\n\nSUMMARY STATEMENTBasement membrane invasion by the C. elegans anchor cell is coordinated by a dynamic gene regulatory network encompassing cell cycle dependent and independent sub-circuits.