Corrigall, D.J.; (2010) Regulation of cell shape during organogenesis. Doctoral thesis , UCL (University College London).

Abstract

Control of cell shape is crucial to the proper development of tissues and organs throughout all metazoan phyla. During organogenesis, patterning molecules are responsible for coordinating tissue remodelling that is in part mediated by cell shape changes, based on tightly controlled rearrangements of the cell cytoskeleton. These coordinated cell shape changes are in turn important for the formation of cell–cell contacts, triggering signal transduction cascades and influencing the patterning information. Precisely how cell shape is regulated in response to higher order patterning signals, and how this shape change itself subsequently impacts upon global tissue patterning, remain intriguing questions. This thesis examines and characterises at the cell-biological level a striking example of cell shape change; the morphogenetic furrow of the developing eye in the fruit fly Drosophila melanogaster. In the furrow, cells show a marked decrease in their apical surface area, and contract along their apico-basal axis. The role of polarity determinants, cytoskeletal machinery and the conserved patterning molecules involved in effecting this cell response are investigated. In particular, this work demonstrates a crucial role for the hedgehog signaling pathway in effecting the cell response. This is achieved through the alleviation of Ci75-mediated transcriptional repression, resulting in the activation of non-muscle Myosin II and the formin diaphanous, together with the F-actin effectors Profilin and Cofilin. It is shown that activation of the hedgehog pathway leads to a range of cell behaviours that appear dependent upon the level of Myosin II activity, ranging from shallow grooves to tube-like structures. These results are discussed with regard to wider developmental contexts such as cell constriction in the vertebrate neural tube, other instances of cell constriction, such as cytokinesis, and in relation to the evolution of eye development in dipterans.

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