Research

Life Sciences & Biotechnology

Title :

Mechanochemical coupling underlying emergence of left-right symmetric somites in zebrafish embryos

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. sundar Ram Naganathan, Tata Institute of Fundamental Research (TIFR), Mumbai, Maharashtra

Timeline Start Year :

2024

Timeline End Year :

2026

Contact info :

Equipments :

Details

Executive Summary :

The vertebrate body plan consists of a left-right symmetric segmented backbone, which emerges through somites during embryo development. A lack of symmetry is associated with scoliosis, a debilitating disorder that affects 4% of the population and 70% of cases. The underlying etiology of scoliosis remains unclear. To address this issue, an interdisciplinary approach will be used, including advanced microscopy, automated data analysis, classic embryology experiments, and collaboration with a theoretical physicist. somites form sequentially and periodically, driven by a segmentation clock, which comprises a network of transcriptional waves modulated by FGF, Wnt, and Retinoic Acid (RA) pathways. Every time the clock stops, a left-right pair of somites form. somite formation is also a mechanical process where upregulation of actomyosin leads to a morphological transformation that separates a somite from unsegmented tissue, resulting in a specific shape and volume. The researchers hypothesize that mechanochemical coupling is required for emergence of a precise somite morphology that is similar across the two sides of the embryo. Zebrafish is an excellent model system to test this hypothesis due to its live imaging and ease of performing various perturbations. Light-sheet microscopy will be performed on live embryos to follow left-right somite formation, and geometric morphometrics-based analysis tools will be developed to quantify precise somite shapes and volumes over time. Atomic force microscopy will be performed to directly infer material properties of single somites. A mechanochemical model will be developed to reveal the role of coupling in emergence of precise and symmetric somites.

Total Budget (INR):

29,27,329

Organizations involved