Building and breaking epithelial integrity in the neural tube: an optogenetic approach (360G-Wellcome-208758_Z_17_Z)

<p>Using an innovative optogenetic approach within the zebrafish neural tube, I will directly explore <strong>how the polarity of individual cells drives the tissue organisation of a whole organ. </strong>In combination with 4D live imaging and functional abrogation, I will use light to specifically and reversibly manipulate apicobasal polarity, cleavage furrow formation and PI3K pathway signalling on a subcellular level. I will assess <strong>how apicobasal polarity and division are interrelated </strong>during morphogenesis of vertebrate epithelial tubes and how this relationship contributes to <strong>tissue integrity.</strong></p> <p>&nbsp;</p> <p>Early zebrafish neuroepithelial divisions are highly predictable and coincident with <em>de novo </em>apicobasal polarisation. This provides a tractable model to assess a potential <strong>feedback loop between apical protein localisation and cleavage furrow positioning</strong> during epithelial <em>establishment. </em>The PI3K pathway is likely key to integrating apicobasal polarity with division. Within <em>established</em> epithelia, PI3K pathway defects are prevalent in cancers. I will manipulate PI3K pathway signalling within individual cells or groups of cells within an otherwise normal zebrafish neural tube. This <em>in vivo</em> method for manipulating cancer-linked signalling will allow me to test whether<strong> apicobasal polarity dysregulation is a cause or consequence of tissue disruption</strong>, providing clues to the cellular mechanisms of disease initiation.</p>