VIVO_MECH_COLL_MIGRA · Biomechanical analysis of in vivo directional collective migration

Biomechanical analysis of in vivo directional collective migration

Directional cell migration is important in physiology and pathology. Molecular mechanisms regulating directional migration are largely studied; but the role of mechanical cues and their interplay with biochemical signals during directional migration is poorly understood. To address this I used Neural Crest (NC) cells, a highly migratory embryonic cell population. Evidence about how chemical cues regulate NC migration has accumulated, but nothing is known about the interaction among these cells and their mechanical environment. This proposal focused on understanding how NC interacts with the mechanical cues from its environment during directional migration in vivo, as well as understanding the molecular nature of this interaction. The aims I developed here were: Aim 1) to study the role of mechanical cues in vivo and their interplay with chemical signals during in vivo NC migration. Aim 2) identify the molecular mechanism by which the mechanical properties of the substrate are sensed and translated as signals into the NC, and to test the role of Nedd9 as a key component of this process. After developing several methods to measure and modify mechanical cues in embryos I discovered that the tissue underneath the neural crest called mesoderm stiffens towards the onset of its migration and that this stiffening triggers the migration of the neural crest. Hence, results from this project provided the first demonstration that collective migration is mechanically triggered in vivo and that embryonic tissues interact in a mechanical level to ensure correct morphogenesis. The neural crest cells migrate all over the embryo to differentiate in a large number of embryonic tissues and any deficiency on its migration may lead to congenital defects, i.e., intestinal aganglionosis and craniofacial malformations. Hence, these results are relevant to understand aetiology of neural crest-related congenital disorders by introducing mechanical cues as new aspects to be considered when studying the biology of these defects. Additionally, as neural crest and cancer cell migration are highly similar, our data is also relevant to our understanding of the mechanical microenvironment of cancer cells. This reveal that our project had an impact not only in the scientific community but also in human health. Finally, this grant was a great experience– it provided me with multidisciplinary collaborations, a complete toolbox to address new scientific questions, and it gave me managerial and leadership skills that I will use to obtain funding and lead my own research group.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз