# Transcriptional regulation of morphogenetic behavior and invasive cell fate specification in C. elegans

> **NIH NIH F31** · STATE UNIVERSITY NEW YORK STONY BROOK · 2021 · $39,534

## Abstract

PROJECT SUMMARY / ABSTRACT
The ability of cells to traverse basement membranes (BMs) is a key part of fertility, development, immunity, and
disease. BM invasion is facilitated through expression of extracellular matrix proteins, upregulation of matrix
metalloproteinases, polarization of the F-actin cytoskeleton, and cell cycle arrest. Precise coordination of these
pro-invasive programs is largely achieved through transcriptional regulation; however, our understanding of the
gene regulatory networks (GRNs) involved is limited due to the lack of model systems in which cell invasion can
be visualized live. Here, I propose to fill this gap in knowledge by utilizing morphogenesis of the Caenorhabditis
elegans uterine-vulval connection as a tractable and visually amenable model to examine cell invasion in vivo.
During development of the hermaphroditic somatic gonad, a specialized uterine cell called the anchor cell (AC)
invades through the underlying BM to connect the uterus to the vulval epithelium. The AC itself is specified in a
cell fate decision event earlier in development, in which two initially equipotent cells diverge via stochastic Notch
asymmetry, giving rise to the presumptive AC and a proliferative ventral uterine (VU) cell. Prior research by our
lab and others has identified six transcription factors (TFs) that regulate AC invasion. These include the basic
leucine zipper TF fos-1 (Fos), the basic helix-loop-helix TF hlh-2 (E/Daughterless), two nuclear hormone
receptors, nhr-67 (NR2E1/Tailless/TLX) and sex-1 (RARB/NR1B2), as well as two zinc-finger TFs, egl-43
(EVI1/MEL1) and mep-1. These TFs appear to be functioning in at least three distinct GRN sub-circuits to
regulate AC invasion, one of which involves NHR-67, which functions upstream of CKI-1 (p21/p27) to induce G1
cell cycle arrest. Remarkably, five of the six pro-invasive TFs function reiteratively during the AC/VU cell fate
decision. These include the three TFs comprising the NHR-67/cell cycle-dependent pro-invasive pathway (EGL-
43S, MEP-1, and NHR-67), as well as HLH-2 and SEX-1, which have predicted binding sites within the nhr-67
promoter. Thus, based on the literature and my preliminary studies, my central hypothesis is that the AC invasive
program is dependent on the function of multiple GRN sub-circuits, one of which modulates cell cycle arrest and
is reiteratively used in AC fate specification. In Aim 1 of this project, I will dissect the cis- and trans-regulation of
AC invasion, focusing on the cell cycle-dependent GRN sub-circuit involving the pro-invasive TF nhr-67/TLX. In
Aim 2, I will examine the roles of pro-invasive TFs that reiteratively function in AC specification and investigate
if cell cycle control is the common denominator underlying these two processes. Cutting-edge functional tools,
including an endogenous protein depletion system and a novel cell cycle state sensor, paired with the ability to
perform high-resolution subcellular visual analyses, will allow f...

## Key facts

- **NIH application ID:** 10212437
- **Project number:** 5F31HD100091-03
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Taylor Kinney
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $39,534
- **Award type:** 5
- **Project period:** 2019-07-20 → 2022-07-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212437

## Citation

> US National Institutes of Health, RePORTER application 10212437, Transcriptional regulation of morphogenetic behavior and invasive cell fate specification in C. elegans (5F31HD100091-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10212437. Licensed CC0.

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