# Molecular drivers of tissue-specific morphogenetic programs

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $443,501

## Abstract

Project summary
Congenital malformations, or birth defects, are the leading cause of death of American children under the age
of nine. Neural tube defects (NTDs) are among the most common and devastating congenital malformations,
and result from a failure of the neural tube to close during early embryonic development. Neural tube closure
requires not only that the paired neural folds raise and fuse together, but also that the neuroectoderm
(precursor to the neural tube), narrows sufficiently for the neural folds to meet along the midline. This critical
narrowing begins during gastrulation and is coupled to a concurrent anteroposterior (AP) extension of the
neuroectoderm that results from the polarized rearrangement of cells into a longer and narrower array. This
process, appropriately termed convergence & extension (C&E), is a highly conserved morphogenetic
mechanism with essential roles in shaping numerous embryonic tissues and establishing the animal body plan.
Neural tube closure and extension of the primary AP embryonic axis are driven by C&E of both the
neuroectoderm and the underlying mesoderm, each of which exhibits a distinct suite of cell behaviors and
contributes actively to axis extension. It remains poorly understood, however, how tissue identity is coordinated
with tissue-specific cell behavior programs.
 Here, we address the tissue-specific morphogenesis underlying axis extension in zebrafish, a model
vertebrate embryo. We recently reported that the TGF- family morphogen Nodal is not only necessary for
C&E gastrulation movements in zebrafish, but also sufficient to promote these cell behaviors in otherwise
naïve zebrafish embryonic explants. By varying the method of Nodal signaling activation, we can drive tissue-
specific C&E of either the neuroectoderm or mesoderm within these explants. Importantly, this allows us to
uncouple morphogenesis of individual tissue layers and distinguish the mechanisms that control cell identity
from those that control cell movement. Each mode of C&E is associated with a specific developmental peak of
Nodal activity and transcriptional profile, leading us to hypothesize that temporal patterns of Nodal activity
define tissue-specific morphogenesis via distinct downstream molecular programs. Using cutting-edge
optogenetic approaches to precisely manipulate Nodal activity, experiments proposed in Aim 1 will test how
variations in temporal signaling dynamics control tissue-specific C&E both in and ex vivo. In Aims 2 and 3, we
will define the specific components of each Nodal-dependent gene expression program that are necessary
and/or sufficient for tissue-specific C&E of the mesoderm and neuroectoderm, respectively. This proposal
leverages the unique advantages of our innovative explant model and optogenetic approaches to identify
genes with novel roles in axis extension, thereby advancing a fundamental understanding of neural tube
closure essential for improved diagnosis, prevention, and treatment strate...

## Key facts

- **NIH application ID:** 10440153
- **Project number:** 1R01HD104784-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Margot L.K. Williams
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $443,501
- **Award type:** 1
- **Project period:** 2022-06-22 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440153

## Citation

> US National Institutes of Health, RePORTER application 10440153, Molecular drivers of tissue-specific morphogenetic programs (1R01HD104784-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10440153. Licensed CC0.

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