Shifting into high gear: how Interstitial Cells of Cajal change the motility pattern of the developing intestine

Nicolas Rémy Chevalier (1) , Yanis Ammouche (2, 3) , Anthony Gomis (2, 3) , Clémence Teyssaire (2, 3) , Pascal de Santa Barbara (4) , Sandrine Faure (4)

1 MSC - Matière et Systèmes Complexes
2 MSC - Matière et Systèmes Complexes
3 Université Paris Diderot, Sorbonne Paris Cité, Paris, France
4 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]

The first contractile waves in the developing embryonic gut are purely myogenic; they only involve smooth muscle. Here, we provide evidence for a transition from smooth muscle to interstitial cell of Cajal (ICC)-driven contractile waves in the developing chicken gut. In situ hybridization staining for anoctamin-1 (ANO1), a known ICC marker, shows that ICCs are already present throughout the gut, as from embryonic day (E)7. We devised a protocol to reveal ICC oscillatory and propagative calcium activity in embryonic gut whole mount and found that the first steady calcium oscillations in ICCs occur on (E14). We show that the activation of ICCs leads to an increase in contractile wave frequency, regularity, directionality, and velocity between E12 and E14. We finally demonstrate that application of the c-KIT antagonist imatinib mesylate in organ culture specifically depletes the ICC network and inhibits the transition to a regular rhythmic wave pattern. We compare our findings to existing results in the mouse and predict that a similar transition should take place in the human fetus between 12 and 14 wk of development. Together, our results point to an abrupt physiological transition from smooth muscle mesenchyme self-initiating waves to ICC-driven motility in the fetus and clarify the contribution of ICCs to the contractile wave pattern. NEW & NOTEWORTHY We reveal a sharp transition from smooth muscle to interstitial cell of Cajal (ICC)-driven motility in the chicken embryo, leading to higher-frequency, more rhythmic contractile waves. We predict the transition to happen between 12 and 14 embryonic wk in humans. We image for the first time the onset of ICC activity in an embryonic gut by calcium imaging. We show the first KIT and anoctamin-1 (ANO1) in situ hybridization micrographs in the embryonic chicken gut. Copyright © 2020 the American Physiological Society

Mots clés: Calcium imaging; Contraction wave; Embryo; Interstitial cells of Cajal; Intestine; Motility; Pacemaker; Smooth muscle

Domaines: Sciences du Vivant [q-bio]

Nicolas Rémy Chevalier, Yanis Ammouche, Anthony Gomis, Clémence Teyssaire, Pascal de Santa Barbara, et al.. Shifting into high gear: how Interstitial Cells of Cajal change the motility pattern of the developing intestine. AJP - Gastrointestinal and Liver Physiology, In press, ⟨10.1152/ajpgi.00112.2020⟩. ⟨hal-02929730⟩