Project leader(s)
Elise Maréchal, 2nd year PhD student
- Thesis title: Identification of pathophysiological mechanisms in congenital cardio-neurocutaneous syndromes
- Type of project: Dissemination (poster)
- Event : New Frontiers in Developmental Biology - Celebrating the Diversity of Life (nov. 2022)
Developmental diseases affecting the skin, the nervous system or the heart have a significant impact on the quality of life and fate of those affected, and I am seeking to identify common biological causes associated with the development of these different diseases. The MAP-K signaling pathway is a set of signals in cells that regulates many different processes, such as cell proliferation or differentiation. Alterations in this pathway, which appear during embryo Training, are responsible for a number of developmental syndromes with very different visible characteristics known as "RASopathies".
Congenital melanocytic nevus is an RASopathy that occurs after a mutation in the MAP-K pathway specifically in melanocytic progenitors, and presents with a spectrum of severity ranging from small, isolated lesions in the skin, to giant, often multiple lesions. I demonstrated the existence of biological differences in patients with severe forms (with increased susceptibility to cancer), providing a new parameter for early diagnosis.
We hypothesized that alterations in the MAP-K pathway could disrupt the development of other tissues. To this end, I have characterized mouse models with disruption of the MAP-K pathway specifically in the peripheral nervous system or heart. My results demonstrate the development of degenerative peripheral neuropathies or severe cardiac defects. Characterization of these models will enable me to improve our understanding of the specific physiological and pathological mechanisms involved in the development of neuromuscular diseases or heart defects.