# Defining Direct and Indirect Roles of Nodal Signaling in Convergence & Extension

> **NIH NIH R00** · BAYLOR COLLEGE OF MEDICINE · 2021 · $186,802

## Abstract

Project Summary
Extension of the anterior-posterior (head to tail) body axis is critical to development of a healthy fetus. Defects
in this process can result in abnormally short embryos, and more importantly, neural tube closure defects
(NTDs). NTDs affect approximately 1 in 1,000 human births, making them one of the most common classes of
congenital birth defects. Despite the significant burden to individuals and society the underlying genetic causes
remain still poorly understood. Therefor, defining the mechanisms of axis extension contributes significantly to
the fundamental study of developmental biology and has important implications in human health. Anterior-
posterior (AP) axis extension occurs via a highly conserved morphogenetic mechanism called convergence
and extension (C&E), which employs polarized cell behaviors such as directed migration and ML cell
intercalation to drive mediolateral (ML) narrowing of the body accompanied by elongation in the AP dimension.
In vertebrate embryos, this occurs during gastrulation, the early embryonic process during which the three
primordial germ layers are established and then shaped into a rudimentary body plan. Patterning of the AP
axis is also required, and in some cases sufficient, for C&E to occur. AP positional identity of a tissue is
established during embryonic axis patterning prior to the onset of gastrulation, but how this is communicated to
the morphogenetic machinery that drives C&E is not understood. This coordination of tissue patterning with
morphogenesis remains one of the most fundamental questions in developmental biology.
 The morphogen Nodal likely occupies a vital position at the interface of tissue patterning and
morphogenesis. In vertebrate embryos, graded Nodal signaling is essential for induction of endoderm and
mesoderm and AP patterning, with higher Nodal levels specifying more dorsal/anterior cells fates. Loss of
Nodal signaling in zebrafish embryos results in severely reduced axial extension and an open neural tube, but
also nearly complete mesoderm deficiency, making it unclear whether extension defects in the neuroectoderm
are due directly to the loss of Nodal signaling or indirectly to the loss of mesoderm. Experimental evidence
suggests an instructive yet indirect role of Nodal signaling during C&E of mesodermal tissues, but the way(s)
by which Nodal signaling regulates C&E is unknown. Here, I propose to test the hypothesis that Nodal
signaling regulates C&E gastrulation movements indirectly via its role in mesoderm specification and
patterning, and aim to define the tissue, cellular, and molecular mechanisms by which Nodal signaling provides
instructive cues for axis extension. Characterization of Nodal's role in this process will significantly increase our
understanding of how tissue patterning is coordinated with morphogenesis in vertebrate embryos and can help
to identify the underlying causes of NTDs.

## Key facts

- **NIH application ID:** 10057264
- **Project number:** 5R00HD091386-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Margot L.K. Williams
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $186,802
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057264

## Citation

> US National Institutes of Health, RePORTER application 10057264, Defining Direct and Indirect Roles of Nodal Signaling in Convergence & Extension (5R00HD091386-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10057264. Licensed CC0.

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