Subventions et des contributions :

Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023)

Malformations involving the facial regions are very common and account for at least one third to half of all human birth defects . Proper development of the facial region is highly dependent on the growth, migration and differentiation of an important population of cells, the cranial neural crest cells (CNCCs). My long range research goal is to characterize the molecular mechanisms of how CNCCs migrate during facial growth. We have previously shown that Flrt2 , a member of the Fibronectin (F) Leucine (L) Rich (R) Transmembrane (T) gene family, was highly expressed in migratory CNCCs and a decrease in cell migration resulted when this protein was knocked down. We also have preliminary data to show that FLRT2 protein interacted with fibronectin (Fn) in the extracellular matrix and Enolase-1 (ENO-1), an enzyme capable of increasing cell motility. We hypothesize, therefore, that Flrt2 regulates migration in CNCCs. The objectives of this application are to, firstly, characterize the interactions of FLRT2 with Fn and ENO-1, and, secondly, to characterize the relationship of Flrt2 with other molecules shown previously to be important in CNCC migration. Various techniques will be employed, e.g., gene and protein expression analyses (immunofluorescence, in situ hybridization, FRET analyses, western blotting), DNA cloning and transfections. We also propose the generation of a CNCC Flrt2 conditional knockout mice to complement the use of cell lines to analyze Flrt2 function. Together, the two aims complement each other and will lead to the generation of new information on Flrt2 function in the context of facial development. New and exciting discoveries in other labs currently focus on the functions of the extracellular part of FLRT2; our data will add significantly new information on the intracellular function of FLRT2, thereby linking the extracellular environment with that of the intracellular machinery during cell migration. My research is moving towards innovative strategies for the development of novel and effective strategies for the regulation of fundamental biological events such as cell migration, wound healing, and cancer progression, all of which will directly benefit the health of all Canadians. Training of HQP in advanced molecular and cell biology of cell-cell and –matrix interactions provided through this project will allow trainees to possess a better appreciation for scientific discoveries and to launch a fruitful career in the Life Sciences.