Philosophy
The current framework for tissue morphogenesis explains how genetic and biochemical information drive cellular mechanics and thereby tissue dynamics. This framework, however, fails to account for: 1) Self-organized emerging behaviors that cannot be explained by upstream genetic information; 2) Cell extrinsic information, including external forces; and 3) Multi-scale feedback interactions. By addressing these gaps, we aim to build a new integrated framework for tissue morphogenesis with generalizable principles, thereby advancing our understanding of organ formation, malformation and regenerative medicine.
Approach
We use zebrafish as a vertebrate model system for tissue morphogenesis. They are small (about 4-5 cm), convenient for husbandry, and for doing classical and modern genetics (including CRISPR-Cas9 mediated gene-editing). Their embryos are optically transparent making them ideal for light microscopy & image analysis. A female fish can lay hundreds of externally fertilized eggs allowing high numbers for experiments, including high-throughput transcriptional profiling (e.g. single-cell RNA sequencing), physical & chemical perturbations, and screens.
We deploy the above integrative approaches to uncover principles of morphogenesis from embryonic tissues. Our current favorite embryonic tissue is the otic epithelium, which, through topological remodeling, gives rise to the adult inner ear (see gif and figure below ). Zebrafish, like us, have inner ears comprising of three semicircular canals whose function is to sense balance and whose shape has been conserved through evolution. Inner ear development is a rich platform to study several conventional and unconventional players of tissue morphogenesis including, cell adhesion, contractility, migration, intercellular & cellular-extracellular matrix (ECM) communication, and pressure & tissue homeostasis. We are currently interested in understanding the roles of the extracellular matrix, multi-scale feedbacks and tissue geometry.
Zebrafish inner ear morphogenesis
Morphogenesis of the semicircular canals from the otic epithelium
(anterior, posterior and lateral canals labelled as 1, 2 and 3 respectively)
Current Projects
The Extracellular Matrix
We explore the roles of the ECM in development and disease using imaging (including development of tools for visualizing the ECM), genetics and perturbations approaches.
Multi-scale feedbacks
We investigate feedbacks between tissue mechanics and gene-expression using quantitative systems approaches (including biophysical perturbations and physical modeling).
Tissue Geometry
We study the respective contributions of tissue geometry and genetic patterns in robust and reproducible tissue morphogenesis using a combination of experiments and theory.