# Dynamical maintenance of left-right symmetry during vertebrate development

> **NIH NIH R01** · BRANDEIS UNIVERSITY · 2024 · $429,313

## Abstract

Broad Objective: Maintaining anatomical symmetry in vertebrates is essential for proper physiological 
function, and loss of symmetry in ribs and vertebrae can lead to serious conditions such as scoliosis and
impairments of appropriate breathing and posture. This project will explore the developmental emergence 
of left-right symmetry, combining biological experiments on wild-type mice and a model of early loss of
symmetry with mathematical models of gene expression and molecule distributions. Through these studies, 
the project will provide new important insight into the determinants of body (a)symmetry. 
Specific Aims and Research Design: The somites are the embryonic structures giving rise to the 
vertebrae and rib cage. They are formed at early phases of embryonic development and emerge 
progressively in pairs of paraxial mesoderm blocks on both sides of the midline in a highly symmetric 
manner. The symmetry of the somites is actively maintained through mechanisms controlled by retinoic 
acid (RA) signaling. Indeed, animals deficient in RA exhibit an asymmetric somite formation. This proposal 
will investigate this RA-mediated symmetry maintenance mechanisms by combining experiments on RA-deficient mice with mathematical models of somitogenesis. 
In Aim 1, to investigate the dynamical mechanism of somite formation in wild-type and RA-deficient 
embryos, we will characterize finely the somite formation timing, period, and positions in mouse embryos 
through live imaging techniques coupled with and topological data analysis. In Aim 2, to study the genetic 
mechanism involved in the segmentation clock, which controls the spatio-temporal formation of somites, 
the same live-imaging setup will be leveraged to extract the dynamics of the segmentation clock in mouse 
embryos. This data will be used to develop and specify a theoretical model of somitogenesis which will in 
turn allow exploring the determinants of symmetry maintenance and its breakdown. To explore how 
asymmetry may arise and be buffered by RA, Aim 3 proposes to study the origin of asymmetry in RA-deficient mouse. It will rely on the development of computational fluid dynamics simulations to analyze the 
global distribution of key signaling molecules as they are transported in fluids driven by cilia movements.
This will be coupled to reaction-diffusion systems and their dynamics will be explored to investigate how 
RA-mediated mechanism can buffer any initial asymmetry in molecular concentrations.

## Key facts

- **NIH application ID:** 10918258
- **Project number:** 5R01GM152811-02
- **Recipient organization:** BRANDEIS UNIVERSITY
- **Principal Investigator:** Jonathan David Touboul
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $429,313
- **Award type:** 5
- **Project period:** 2023-09-05 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10918258

## Citation

> US National Institutes of Health, RePORTER application 10918258, Dynamical maintenance of left-right symmetry during vertebrate development (5R01GM152811-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10918258. Licensed CC0.

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