Intern seminars : Olivier Romito and Nathan Martin-Fournier

Stage-dependent roles of calcium signaling in melanoblast migration and maturation, Olivier Romito

Neural crest cells are highly migratory stem cells that give rise to a wide variety of derivatives, including melanocytes, the pigment-producing cells of the skin. Their precursors, melanoblasts, migrate and colonize the embryonic skin of mice between E9.5 and E14.5, notably throught the activation of the endothelin-3 (ET-3) pathway, which acts between E10.5 and E12.5. We previously showed that ET-3 induces IP3 receptors (IP3R) and T-type calcium channels (CaV T) dependent Ca²⁺ oscillations in enteric neural crest cells. To date, the role of Ca²⁺ signaling in melanoblast development has never been examined.

Here, we show that Ca²⁺ oscillations emerge progressively over the course of melanoblast development, paralleling an increase in IP3R expression. Although largely absent at early stages (E11.5-E13.5), oscillations can be triggered at these stages by exogenous ET-3 through an IP3R- and CaV T-dependent mechanism, indicating that the Ca²⁺ machinery is already functional but requires a sufficient ligand concentration to be activated. Consistent with its early window of action, the inhibition of ET-3 pathway blocks melanoblast migration at E11.5 but not at E13.5. Blocking IP3R and CaV T has only a marginal effect on melanoblast migration at E13.5. By E18.5, Ca²⁺ oscillations are robust and relying on IP3R activity independently of plasma membrane Ca²⁺ channels. In human, IP3R expression correlates positively with melanogenic enzyme expression, pointing to a role for these oscillations in melanocyte maturation.

Together, these findings reveal that Ca²⁺ signaling changes dynamically throughout melanoblast development, potentially contributing to cell migration and to melanocyte maturation.

MSC platform dedicated to mecanobiology, Nathan Martin-Fournier

This seminar, made mostly for students (but which could be interesting to non-students as well), aims at giving a tour of the different experimental setups for mechanobiology available at MSC and its vicinity. These setups either allow the application of controlled mechanical contraints on biological samples, or the measurements of force, rigidity or viscosity at a microscopical scale. Maybe these systems will be useful to you in your research work?