# Modeling and analysis of BMP-mediated Dorsal/Ventral patterning in zebrafish embryos

> **NIH NIH R01** · PURDUE UNIVERSITY · 2020 · $344,839

## Abstract

Project summary
Bone Morphogenetic Proteins (BMPs) function as morphogens during development to specify spatial
organization of embryonic axes and organ structures. Numerous extracellular antagonists and co-factors work
in concert to dynamically control BMP signaling distributions along the dorsal-ventral (DV) embryonic axis in
vertebrates to induce space and time-dependent patterns of gene expression. As the embryo progresses from
the blastula stage into the gastrula stage, zygotic feedback in response to BMP signaling begins and cells start
to play an active role by simultaneously responding to BMPs and regulating the secretion of antagonists and
other factors that shape the BMP gradient. However it is not well understood how the system dynamically
regulates pattern formation. Studies of gastrula stage BMP pattern formation provide an ideal context to
unravel how feedback regulation shapes the gradients of BMP signaling in a vertebrate system. We
hypothesize that BMP-mediated feedback by admp, sizzled, tld, and bambi dynamically shape the gradient in
gastrula embryos. Our objective is to delineate how coupled patterning and feedback shape gradients and
discover mechanisms of BMP regulation in zebrafish gastrula. In Aim 1 we will quantify spatiotemporal BMP
signaling and feedback target gene expression in wild-type and mutant zebrafish gastrula embryos.
Furthermore, we will measure phospho-Smad 1/5 (PSmad) levels in toto in wild-type (wt) gastrula embryos,
and develop our new wavelet-based segmentation and image analysis software WaveSeg
(https://waveletseg.weebly.com) to quantify, segment, and register the data. This work will provide the first-
ever quantitative data needed to identify feedback relationships that shape the PSmad gradient. Quantification
of BMP patterning in gastrula stage embryos will provide insight into the role of feedback in gradient refinement
in a rapidly changing spatial domain. In Aim 2 we will develop a 3-dimensional growing mesh finite element
model of BMP pattern formation in gastrula stage embryos. Evaluation of the models against quantitative
imaging data provides a rigorous basis to discern the mechanisms of gastrula embryo pattern formation and
generate new tests to validate or refute the consistent mechanisms. The seamless integration and back-and-
forth between imaging, genetics, and modeling will elucidate how the extracellular BMP pathway factors
modulate the BMP signaling gradient. Lastly, in Aim 3 we will investigate the feedback loops in BMP signaling
that have been proposed to provide embryonic scale invariance, robustness with respect to partial loss of
network components, and increase the dynamic range of signal interpretation. Understanding these networks
of BMP regulation will provide insight into BMP function in other contexts including organogenesis, cancer
metastasis, angiogenesis and development.

## Key facts

- **NIH application ID:** 9985964
- **Project number:** 5R01GM132501-02
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** David Michael Umulis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $344,839
- **Award type:** 5
- **Project period:** 2019-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985964

## Citation

> US National Institutes of Health, RePORTER application 9985964, Modeling and analysis of BMP-mediated Dorsal/Ventral patterning in zebrafish embryos (5R01GM132501-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9985964. Licensed CC0.

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