Gene regulation and morphogenesis

Establishment of cell polarity and its relationship to signaling.

Summary

The interest of my laboratory is to understand how cell polarity influences cell behaviour and organism morphogenesis. All cells are polarized to a certain extent, which, depending on the cell type, results in an asymmetric distribution of molecules and organelles, creating different functional domains. There are polarity determinants involved in generating the different functional domains generate and maintain this polarity; cell trafficking proteins are involved in the movement of proteins and lipids between these functional domains; and cytoskeleton regulators, over which these functional domains are created and molecules are driven. Polarity is essential in morphogenesis, not only it controls cell homeostasis, but it also coordinates movements and shape changes required for the cell to integrate in the tissue and for the organogenesis to progress properly. Cell polarity control depends on the same signalling pathways regulating morphogenesis. However, this control is bidirectional as cell polarity is able to modulate signaling by influencing ligand secretion and receptor localization in the cell or by recruiting or sequestering signaling pathway components. My group has contributed to clarify how the cell determinant aPKC establishes and maintains cell polarity in Drosophila melanogaster, and to understand how cell polarity regulates JAK/STAT signaling in Drosophila’s epithelia. On the other hand, we have unravelled a new link between cell polarity and trafficking at the level of aPKC’s recycling by the Nuf-Rab11 complex, a process essential to maintain epithelia homeostasis.  

 

Figure. Scheme showing the main cell polarity complexes. A) Drosophila embryonic epithelial cells showing polarized subcellular localization of the aPKC apical polarity determinant and the Scribble basolateral protein. B) In the WT aPKC localizes in apical whilst Scrib is basolateral. Overexpression of a dominant negative aPKC version (CAAXDN) affects cell polarity relocalizing Scribble to apical. C-D) Removal of aPKC’ interferes with cell polarity affecting the morphogenesis of structures as shown here for the Drosophila wing.


Recently we have described a new conserved function of Drosophila’s RhoGAP Cv-c and its human ortholog DLC3 for testis’ organization.
We have demonstrated that Cv-c mutations similar to those on DLC3 linked to human testicular dysgenesis affect the testis organization preventing mesodermal cells to retain germ cells inside the testis.


                                                  

Figure. Mesodermal cells in Drosophila and vertebrate testis are necessary for retaining the germ cells at the end of embryogenesis. Mesodermal cells signal and support germ cells (green) forming an extracellular cell matrix (white, left) surrounding the testis. In RhoGAP cv-c’ mutants this association is not maintained, the gonad breaks and the germ cells escape from the testis (green, right). Human DLC3, cv-c’ ortholog, is involved in testis formation during embryogenesis and its mutation results in 46X,Y dysgenesis.


Our current line of work combines molecular and cellular biology technics with Drosophila melanogaster genetics to: on the one hand, study the connexion between cell trafficking with the establishment and maintenance of cell polarity; and, on the other hand, decipher how cell polarity regulates organogenesis.

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