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Mechanobiology of organ development and homeostasis

Biology Colloquium | Dr. Priti Agarwal | Aug 7th, 2023

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Abstract:

Organ morphology is critical for its function. Mechanical signals and biochemical cues influence cell and tissue behavior to shape an organ during development. Although significant advances have been made in understanding the genetic regulation of 3D organ development, the role of mechanical forces are not fully understood. I use Caenorhabditis elegans to decipher the mechanical basis of organ development – using gonad development as a model. The C. elegans gonad has two symmetrical U-shaped arms, each with a single somatic cell called a Distal tip cell (DTC) at its tip. The DTC functions as a leader cell guiding follower germ cells to form the U-shaped architecture. Using live-imaging, laser ablation, DTC-specific genetic manipulation, and a qualitative physical modeling, I discovered that the gonad elongates not by the pulling force of the leader cell migration, but rather due to a pushing force generated by proliferating germ cells confined behind the DTC. Local release of matrix-degrading metalloproteases by the DTC determines the direction of gonad elongation. Moreover, asymmetric DTC-ECM adhesion creates torque that drives the U-turning of the gonad. Taken together, this study provides novel mechanistic insight into organ morphogenesis which may also be relevant for other developmental systems as well as solid tumor metastasis.

 

About the speaker:

Dr. Priti Agarwal is a Research Fellow at Tel Aviv University, Israel. She combines C. elegans genetics, quantitative fluorescence microscopy, and microfluidics to understand the mechanics of organ development. Priti has a Ph. D from IIT, Kanpur and thereafter worked at the Mechanobiology Institute, Singapore before moving to the Department of Cell and Developmental Biology at Tel-Aviv University. 

 

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