# Cell Cycle Regulation of Cell Fate and Morphogenesis in D. rerio

> **NIH NIH F31** · STATE UNIVERSITY NEW YORK STONY BROOK · 2022 · $36,468

## Abstract

PROJECT SUMMARY / ABSTRACT
Complex morphogenetic processes are required for proper organismal development. These morphogenetic
processes require various combinations of cell migration, proliferation, invasion, and fate acquisition. The
coordination of these behaviors must be tightly regulated, as dysregulation of these processes can lead to
developmental disorders and disease states such as cancer. To study the regulation of complex
morphogenetic process we turn to zebrafish development. In zebrafish, morphogenesis of midline tissue
structures such as the notochord, floor plate, and hypochord drive axis elongation of the developing embryo.
These tissues are derived from a population of progenitors residing in the tailbud known as midline progenitor
cells (MPCs). MPCs undergo a morphogenetic process called convergent extension (CE) to give rise to the
notochord. During CE, adjacent MPCs migrate and intercalate between one another to form the notochord.
The decision of MPCs to adopt a notochord, floor plate, or hypochord fate is based on local signaling cues
such as Wnt and Notch. While these signaling pathways have been shown to regulate morphogenetic cell
behaviors, there is growing evidence to suggest that the cell cycle can also modulate cell behaviors. However,
the mechanisms by which cell cycle state dictates cell behavior and cell fate during tailbud morphogenesis
remain unclear. I will address this gap in knowledge and elucidate the relationship between cell cycle state and
cell fate/morphogenesis during development using CE of the zebrafish notochord during tailbud
morphogenesis as a model. Published data from my lab and others show notochord progenitor cells are in G1,
while floor plate and hypochord progenitors can be found in all phases of the cell cycle. Furthermore, these
notochord progenitors undergo CE in G1 and reenter the cell cycle after joining the notochord, suggesting that
G1 arrest facilitates this morphogenetic process and notochord fate acquisition. In Aim 1 of this project, I will
perturb G1 arrest specifically in the MPCs and determine the effects on CE. Using transgenic zebrafish lines,
including a CDK activity biosensor to establish cell cycle state, and spinning disk confocal microscopy, I will
time-lapse image these cell cycle perturbed embryos and quantify CE and fate acquisition. In Aim 2, I will
explore the gene regulatory network (GRN) responsible for inducing G1 arrest in the MPCs, with a focus on the
T-box transcription factor Brachyury (tbxta). Published data show tbxta to be indispensable to notochord
formation and moreover, preliminary data from our lab show knockdown of tbxta drives notochord progenitors
to cycle and be excluded from the notochord, adopting a floor plate or hypochord fate. The combination of a
CDK activity biosensor, cell cycle perturbation constructs, midline directed cell transplantation, and spinning
disk confocal microscopy will allow me to test my hypotheses thoroughly and rigorously.

## Key facts

- **NIH application ID:** 10463258
- **Project number:** 1F31HD108921-01
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Samantha Stettnisch
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $36,468
- **Award type:** 1
- **Project period:** 2022-05-19 → 2025-05-18

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463258

## Citation

> US National Institutes of Health, RePORTER application 10463258, Cell Cycle Regulation of Cell Fate and Morphogenesis in D. rerio (1F31HD108921-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10463258. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*