Calcium wave dynamics in the embryonic mouse gut mesenchyme: impact on smooth muscle differentiation

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Chevalier, Nicolas | Zig, Léna | Gomis, Anthony | Amedzrovi Agbesi, Richard | El Merhie, Amira | Pontoizeau, Laetitia | Le Parco, Isabelle | Rouach, Nathalie | Arnoux, Isabelle | de Santa Barbara, Pascal | Faure, Sandrine

Edité par CCSD ; Nature Publishing Group -

International audience. Abstract Intestinal smooth muscle differentiation is a complex physico-biological process involving several different pathways. Here, we investigate the properties of Ca 2+ waves in the developing intestinal mesenchyme using GCamp6f expressing mouse embryos and investigate their relationship with smooth muscle differentiation. We find that Ca 2+ waves are absent in the pre-differentiation mesenchyme and start propagating immediately following α-SMA expression. Ca 2+ waves are abrogated by Ca V 1.2 and gap-junction blockers, but are independent of the Rho pathway. The myosine light-chain kinase inhibitor ML-7 strongly disorganized or abolished Ca 2+ waves, showing that perturbation of the contractile machinery at the myosine level also affected the upstream Ca 2+ handling chain. Inhibiting Ca 2+ waves and contractility with Ca V 1.2 blockers did not perturb circular smooth muscle differentiation at early stages. At later stages, Ca V 1.2 blockers abolished intestinal elongation and differentiation of the longitudinal smooth muscle, leading instead to the emergence of KIT-expressing interstitial cells of Cajal at the gut periphery. Ca V 1.2 blockers also drove apoptosis of already differentiated, Ca V 1.2-expressing smooth muscle and enteric neural cells. We provide fundamental new data on Ca 2+ waves in the developing murine gut and their relation to myogenesis in this organ.

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