Building an integrated framework for tissue morphogenesis with the zebrafish inner ear
Monday, November 7, 2022 - 4:15pm
Schultz 107
Quantitative & Computational Biology
LSI - Genomics

How simple tissues give rise to geometrically complex organs with robust shapes and functions is a fundamental question in biology. The current mechanistic framework explains how upstream genetic and biochemical information patterns cellular mechanics to drive tissue dynamics. In this framework, the main driving force is cell-intrinsic and generated by actomyosin contractility. The extracellular matrix (ECM) that surrounds most cells is considered to be a passive mechanical scaffold that may shape these forces through differential stiffness. I will present a case that inverts this expectation. Zebrafish semicircular canals form from invaginations in the otic epithelium (buds) that extend and fuse to form the hubs of each canal. We find that conventional actomyosin-driven behaviors are not required. Instead, local secretion of hyaluronan, made by the enzymes ugdh and has3, drives canal morphogenesis. Charged hyaluronate polymers osmotically swell with water and generate isotropic extracellular pressure to deform the overlying epithelium into buds. The mechanical anisotropy needed to shape buds into tubes is conferred by a polarized distribution of cellular protrusions, linked between cells, that we term cytocinches. Hyaluronate-pressure shaped by anisotropic tissue stiffness may be a widespread mechanism for powering morphological change in organogenesis and tissue engineering.

In our lab, we use the zebrafish inner development to investigate emerging behaviors in tissue morphogenesis as a result of under-explored players such as the mechano-chemical roles of the ECM, feedback interactions between patterning and morphogenesis, and the contribution of tissue geometry in determining robust organ shape. Our long-term vision is to build an integrated framework for tissue morphogenesis encapsulating reciprocal flow of information between genetic-patterns, cellular mechanics, tissue dynamics, and organ geometry for successful embryonic development.

 Akankshi Munjal

Dr. Munjal completed her undergraduate studies at the University of Delhi, and her master's at the National Centre for Biological Sciences (NCBS) in Bangalore, one of India’s finest interdisciplinary institutes. She then moved to France to do her PhD at Aix Marseille University with Prof. Thomas Lecuit where she studied the early development of fruit fly embryos and discovered a self-organized mechanochemical network that drives shape changes during morphogenesis. After moving to the US for her postdoc with Prof Sean Megason at Harvard, she continued in the field of tissue morphogenesis with zebrafish embryos. Here she was an HFSP long-term fellow and was later awarded the K99/R00 transition to independence award by the NICHD. She recently started her lab at Duke University as a Whitehead Scholar. The Principles of Tissue Morphogenesis Lab is driven by curiosity and is striving to build an inclusive environment for trainees from diverse backgrounds.

Hosted by Celeste Nelson