Shaping and moving living structures: the importance of being (morphodynamically and mechanically) heterogeneous

Tissues, the distinguishing feature of multicellular organisms, are complex, dynamic, intricately patterned, mechanically and chemically connected cellular assemblies. Epithelia, tissues that form outer barriers or inner linings of organs and organisms, are deformable cell sheets that can stretch, bend, invaginate and tubulate to generate new shapes, create layers and form tubes with branches. Epithelial sheet deformation relies on rich heterogeneities in the shapes and dynamics of their constituent cells. What guides the stereotypical epithelial sheet deformations that sculpt the tissues and body plans of organisms? What confers cells within epithelial sheets their characteristic dynamics? How are the morphodynamic properties of cells ordered in space and time to enable tissues to be sculpted to their final shapes and positioned at their final destinations? How much are these decisions influenced by genetic pre-patterns (top-down control by gene regulatory networks) and the mechanical microenvironment (bottom-up control by cell interactions with neighbours and substrates). Do genetic prepatterns (gene expression, protein distribution, molecular interactions) and mechanical properties (tension, compression, shear, stiffness, fluidity) feedback regulate each other? How do they do so? These questions, fundamental to our understanding of the generation of tissue form (morphogenesis) and function, are at the interface between developmental biology, cell biology and soft matter physics and have been the focus of my lab’s research. 

In my talk, I will discuss our work over the years, that has exploited the rich diversity as well as the tractability of morphogenesis in the fruitfly, Drosophila melanogaster, to understand the molecular, cellular and physical principles that underlie the formation of stereotypic cellular patterns or morphological motifs (seams and boundaries, rosettes and placodes) during embryonic development and their influence on tissue dynamics and mechanics. These questions are also of outstanding clinical importance.

References:

Nandi S, Balse A, Inamdar MM, Krishnamurthy V and Narasimha M. 2022. Actomyosin cables position cell cohorts during Drosophila germband retraction by entraining their morphodynamic and mechanical properties. bioRxiv 2022. doi: https://doi.org/10.1101/2022.09.23.509113.

Dasgupta PTand Narasimha M. 2019. Cytoskeletal tension and Bazooka/Par3 tune interface geometry to ensure fusion fidelity and epithelial continuity during Drosophila dorsal closure. eLife 2019. DOI: 10.7554/eLife.41091

Meghana C, Hameed FM, Ramdas N, Rao M, Shivashankar GV, Narasimha M (2011) Integrin adhesion
drives the emergent polarization of active stresses to pattern the dynamics of delamination. Proceedings of the National Academy of Sciences USA 108:9107. https://doi.org/10.1073/pnas.1018652108