Stem cells are important for the maintenance and repair of tissues, as exemplified by the role of satellite cells in muscle. Diseases that perturb these cells can have severe consequences. For example, muscular dystrophies are a group of genetic diseases that affect the skeletal muscles and often the heart and one cause of dystrophy is a failure of adult muscle stem cells (satellite cells) to compensate for aging or injury. This most likely occurs because, the satellite cells are constantly recruited to repair the muscles and so their regenerative capacity may become exhausted with time. One key pathway implicated in the maintenance and regulation of many stem cells, including satellite cells is the Notch pathway (N). The function of N is conserved in Drosophila, which offers many advantages for dissecting the molecular mechanisms downstream of Notch, most notably the lack of redundancy and the genetic tractability. The goal of my researches is to find out how N regulates the Drosophila muscle precursors and prevent them from premature differentiation.
By combining genome-wide and genetic studies, I hope to identify key components of the regulatory network downstream of Notch in these cells. Since genes are conserved between humans and flies, new knowledge in flies might hold a great deal of promise to understand the mechanisms involved in sustaining muscle progenitors that has the potential in turn to help elucidate pathological mechanism involved in muscular dystrophies.
Prof Sarah Bray
Dr Evanthia Zacharioudaki
Dr Kat Millen
Hadi Boukhatmi, Christoph Schaub, Laetitia Bataillé, Ingolf Reim, Jean-Louis Frendo, Manfred Frasch, Alain Vincent, (2014), An Org-1–Tup transcriptional cascade reveals different types of alary muscles connecting internal organs in Drosophila, Development, 141, 3761-3771
Guillaume Pézeron, Kat Millen, Hadi Boukhatmi, Sarah Bray, (2014), Notch directly regulates the cell morphogenesis genes Reck, talin and trio in adult muscle progenitors, Journal of cell science, 127, 4634-4644
Hadi Boukhatmi, Jean Louis Frendo, Jonathan Enriquez, Michèle Crozatier, Laurence Dubois, Alain Vincent, (2012), Tup/Islet1 integrates time and position to specify muscle identity in Drosophila, Development, 139, 3572-3582
Jonathan Enriquez, Hadi Boukhatmi, Laurence Dubois, Anthony A Philippakis, Martha L Bulyk, Alan M Michelson, Michèle Crozatier, Alain Vincent, (2010), Multi-step control of muscle diversity by Hox proteins in the Drosophila embryo, Development, 137:457-466