Extrinsic and intrinsic control of cell shape and polarity.
Doctoral thesis, UCL (University College London).
Since physical form and function are intimately linked, mechanisms that maintain cell shape and size within strict limits are likely to be important for a wide variety of biological processes. However, while intrinsic controls have been found to contribute to the relatively well-defined shape of bacteria and yeast cells, the extent to which individual cells from a multicellular animal control their plastic form remains unclear and is the subject of much scientific interest. In this work I studied the regulation of the cell length using micro-patterned lines to limit cell extension to one dimension. In particular, I described a mechanism by which animal cells maintain a characteristic steady-state length independent of their size, pattern-width and cortical actin, but dependant on microtubule dynamics and organization. Population of dynamic microtubules aligned along the long cell axis, as the result of interactions of microtubule plus ends with the lateral cell cortex, drives elongation of cells on micropatterned lines. Furthermore, I described a mathematical model of micropatterned cells based on microtubules dynamics. Notably, the model recapitulates the cell length control mechanism that I observed experimentally. Moreover, I discuss model predictions and related experimental tests validating these predictions and confirming the cell length control hypothesis. In conclusion, my work suggests that microtubules impose unexpected limits on cell geometry that enable cells to regulate their length. Since cells are the building blocks and architects of tissue morphogenesis, such intrinsically-defined limits may be important for development and homeostasis in multicellular eukaryotes. Finally, preliminary in-vivo experiments confirmed the biological relevance of the homeostasis cell length control in zebra fish.
|Title:||Extrinsic and intrinsic control of cell shape and polarity|
|Additional information:||Permission for digitisation not received|
|UCL classification:||UCL > School of BEAMS > Faculty of Maths and Physical Sciences > CoMPLEX - Maths and Physics in the Life Sciences and Experimental Biology|
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