# Inductive and morphogenetic processes shaping the zebrafish embryonic axes

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2021 · $673,234

## Abstract

ABSTRACT
The overall goal of this Maximizing Investigator’s Research Award renewal application is to advance
understanding of how inductive and morphogenetic processes during vertebrate embryogenesis are coordinated
to ensure normal development. Early inductive processes controlled by maternal and zygotic gene products
establish embryonic polarity and germ layers, while convergence and extension (C&E) gastrulation movements
elongate embryonic tissues down the anteroposterior axis and narrow them mediolaterally. The noncanonical
Wnt/Planar Cell Polarity (Wnt/PCP) signaling pathway polarizes morphologies and behaviors of mesenchymal
gastrula cells that shape embryonic body. We previously proposed that Wnt/PCP signaling acts as a cellular
compass that orients cells with respect to the anteroposterior embryonic axis, but how the compass is regulated
is not understood. During the previous funding period, we surprisingly found that several pathways work in
parallel to Wnt/PCP to polarize cells during C&E. We also implicated in C&E another conserved regulator of
planar polarity, Dachsous atypical cadherin, which is essential for many processes, including embryonic
cleavages and axis specification, by promoting microtubule dynamics. We invested significant effort in generating
new genetic tools to probe the mechanisms of the Wnt/PCP compass and initiated a genetic screen for new
gastrulation regulators.
 These findings and tools motivate our future studies in three research themes. In the first, we will investigate
how numerous membrane receptors, including Gpr125 adhesion GPCR, which we implicated in the Wnt/PCP
compass, interact during C&E. Using precise mutations and tags in the endogenous gpr125 locus, proteomic
and genetic experiments, we will test whether Gpr125 promotes formation of Wnt/PCP complexes composed of
select components. In the second theme, we will extend our studies of Dachsous and investigate whether it
regulates gastrulation movements by promoting microtubule dynamics. Using Dachsous endogenously tagged
with GFP, we will carry out proteomic studies to isolate endogenous interactors, and genome editing to define
its critical regions. In a parallel unbiased genetic approach, we will continue a promising genetic screen for
maternal and maternal-zygotic mutations that impair embryogenesis and gastrulation. Altogether, our
mechanistic studies of Wnt/PCP and Dachsous regulators of planar cell polarity and unbiased genetic screens,
will both advance the MIRA mission and understanding how inductive and morphogenetic processes are
coordinated during vertebrate gastrulation. As mutations in the components of these pathways cause
miscarriages, birth defects and diseases, our studies will provide insights into their understanding and diagnosis,
and facilitate development of therapies.

## Key facts

- **NIH application ID:** 10207136
- **Project number:** 2R35GM118179-06
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** LILIANNA SOLNICAKREZEL
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $673,234
- **Award type:** 2
- **Project period:** 2016-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10207136

## Citation

> US National Institutes of Health, RePORTER application 10207136, Inductive and morphogenetic processes shaping the zebrafish embryonic axes (2R35GM118179-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10207136. Licensed CC0.

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