Completed Cells, Biochemistry & Physiology Genetics & Molecular Biology

Deciphering morphogenetic cues encoded in cell shape

In plain English

AI plain-English summary

A cell’s shape is not just a container for its contents—it may be an active instruction manual that tells the cell when to divide, what to become, and where to move. This research challenges the long-held assumption that cell shape changes during tissue formation are merely a consequence of other processes. Instead, the researcher proposes that specific cell geometries themselves encode critical signals that direct how tissues build themselves. The problem is that we do not understand how shape influences fundamental decisions like whether a cell divides symmetrically or asymmetrically, how quickly it commits to a fate, or how it orients its movement within a growing tissue. If this project succeeds, it would redefine a basic principle of developmental biology. The findings could eventually inform tissue engineering and regenerative medicine—for example, designing scaffolds that use geometry to guide stem cells into specific shapes and therefore specific fates, improving the repair of damaged blood vessels or nerves. Because cell shape change is universal in developing tissues, the mechanisms uncovered here may be broadly conserved and therapeutically relevant across many organ systems.

View original technical description
Tissue morphogenesis is associated with dramatic changes in cell morphology. Whilst these cell shape changes may define final tissue form, how they impact and/or direct other key morphogenetic processes remains unclear. I aim to redefine our understanding of the role of cell shape in tissue formation by revealing that, far from simply a structural feature, cell shape encodes critical instructive information that directs diverse morphogenetic events. Using the vasculature and neural crest as morphogenetic models and combining zebrafish live-cell imaging, in-vitro micropatterning and computational modelling, this proposal will investigate (1) if acquisition of specific cell geometries in interphase determines whether cells will divide symmetrically or asymmetrically to direct post-mitotic cell fate, (2) whether signal-induced cell shape changes create positive-feedback that amplifies signal to expedite fate decisions, and (3) how local cell shape remodelling, driven by polarised mRNA targeting and translation, functions to orient motile cell polarity and tissue movements. As such, this work will determine if cell shape unexpectedly encodes diverse morphogenetic cues that direct fundamental decision-making processes underpinning tissue building. Considering that cell shape change is an inherent feature of almost all forming tissues, mechanisms uncovered here may be broadly conserved and of therapeutic relevance in numerous tissue contexts.

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Researchers

Shane Herbert (EPMC Awardee)

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Original classification

Senior Research Fellowship

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