Subventions et des contributions :

Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2018-2019)

The long-term goal of my NSERC Discovery research program is to address the fundamental question in the Natural Sciences of how cells receive and respond to signals from their surrounding environment and from neighbouring cells during tissue development. As part of our efforts to fulfill this goal, we have examined molecular mechanisms involved in reciprocal and paracrine modulation of two major skin cell types by growth factor signals: Melanocytes and keratinocytes.

Melanocytes are pigment-producing cells derived from neural crest cells. In the embryo, neural crest cells constitute a unique, transient and multipotent progenitor cell population with high migratory capacity. These cells differentiate into several lineages, including pigment-producing melanocytes, neurons, glial cells and cardiac cells. A subset of neural crest cells that migrate dorso-laterally from the neural tube towards the ventral abdomen and limbs become melanoblasts. Melanoblasts in turn are progenitor cells that later give rise to postnatal melanocyte stem cells and fully mature, melanin-producing melanocytes. Our short-term objectives are:

1. To investigate the role of integrin-linked kinase (ILK) in melanoblast homing and differentiation in vivo. This objective will determine melanoblast responses during migration from the neural crest to ventral regions across the dermis and establish how ILK participates in these processes.

2. To analyze how ILK participates in melanocytic cell responses to paracrine stimuli and cell-cell interactions. This objective will analyze molecular mediators of key melanocyte functions elicited by paracrine stimulation from neighbouring keratinocytes.

   We will use genetically engineered reporter mouse models in which we will specifically inactivate the Ilk gene in melanoblasts and their progeny, for lineage-tracing studies in vivo . We will also use primary melanocytic cell cultures and tissue explants to identify at the cellular and molecular level the contribution of various signalling networks to melanocyte survival, differentiation and ability to respond to paracrine stimuli from neighbouring epithelial cells. Deciphering the pathways and networks that control responses of melanocytic lineage cells to their surrounding environment and to paracrine signals produced by neighbouring cells will provide key insight into the processes involved in development and function of many essential tissues, including those derived from neural crest cells.