06-P042 Tshz3 deficiency causes functional renal tract obstruction by impeding ureteric smooth muscle differentiation

Mechanisms implied in tissues response to the oxygen partial pressure remain poorly understood as well as the role of hypoxia in developmental processes. However, the activation of transcription factors such as FoxO and HIF and the recruitment of signalling pathways including Calcineurin, PI3K, p38-MAPK and mTOR are known to be involved in hypoxia responses. Currently, little information is known about the involvement of signalling pathways generated by these proteins during development. Nevertheless, HIF deficiency in mouse leads to a developmental delay, diseases in neural ridges and placenta formation leading to an early lethality, and fewer somites. In vertebrates, somites segment and subdivide to form the dermomyotome that give the dermis and skeletal muscles. Under the influence of MyoD and Myf5, myotomal cells differentiate in myoblastes. Plasmalems fuse under the influence of Myogenin, to form a myotube that will differentiate in muscle fibre with the expression of MRF4. To understand hypoxia influences during myogenesis and to identify the involved signalling pathways, a developmental model (Xenopus laevis) was used. Analyses of embryos indicate that hypoxia play a role in the survival and the embryonic growth without affecting the formation of somites. However, a decrease in the expression of the muscular markers 12/101 and F59 highlights a default in the differentiation of myotome cells. These results indicate that the oxygen could be involved in a signalling pathway that controls the myogenic differentiation during early development.