The systems developmental biology of zebrafish body elongation

NIH RePORTER · NIH · R35 · $632,313 · view on reporter.nih.gov ↗

Abstract

This research program focuses on the systems developmental biology, biophysics and biomechanics of early spinal column development. The research program utilizes zebrafish as model for understanding the mechanisms of human development and causes of birth defects such as scoliosis and spina bifida. The experimental approach is driven by the idea that quantitative in vivo analysis will lead to fundamental insights into the emergence of biological organization from the collective interaction of its constituent parts. The research program combines genetics, embryology, in vivo biophysics, live imaging and systems level data analysis and computational modeling to study pattern formation and morphogenesis. The proposed research program will address a number of questions regarding biological order and the reproducibility of embryonic development. The program will follow-up on the lab’s recent finding that a dynamically stable pattern of cell state transitions underlies the reproducibility of development to understand the mechanisms maintaining dynamic stability during zebrafish body elongation. The research program will also examine the mechanism of mechanical information regulating the flux of cells through a developmental trajectory. The program will address how tissue-tissue interactions constrain cell behavior during body elongation. At the molecular and cellular level, the program will utilize newly developed methods for in vivo single molecule biophysics to study cell adhesion protein dynamics and their relation to cell state transitions and cell morphology. Overall, this is multi-scale research program that considers the roles of molecules, cells and tissues in the genesis of order in the developing embryo.

Key facts

NIH application ID
10757397
Project number
5R35GM148348-02
Recipient
YALE UNIVERSITY
Principal Investigator
SCOTT A HOLLEY
Activity code
R35
Funding institute
NIH
Fiscal year
2024
Award amount
$632,313
Award type
5
Project period
2023-01-01 → 2027-12-31