Distribution map of peristaltic waves in the chicken embryonic gut reveals importance of ENS and inter-region cross talks along the gut axis

Abstract

Gut peristaltic movements recognized as the wave-like propagation of a local contraction are crucial for effective transportation and digestion/absorption of ingested materials. Although the physiology of gut peristalsis has been well studied in adults, it remains largely unexplored how the cellular functions underlying these coordinated tissue movements are established along the rostral-caudal gut axis during development. The chicken embryonic gut serves as an excellent experimental model for elucidating the endogenous potential and regulation of these cells since peristalsis occurs even though no ingested material is present in the moving gut. By combining video-recordings and kymography, we provide a spatial map of peristaltic movements along the entire gut posterior to the duodenum: midgut (jejunum and ileum), hindgut, caecum, and cloaca. Since the majority of waves propagate bidirectionally at least until embryonic day 12 (E12), the sites of origin of peristaltic waves (OPWs) can unambiguously be detected in the kymograph. The spatial distribution map of OPWs has revealed that OPWs become progressively confined to specific regions/zones along the gut axis during development by E12, and that such specific zones are largely conserved between different individuals implying genetic regulation for OPW determination. We have also found that the enteric nervous system (ENS) is essential for the OPW patterning since an ablation of ENS or blocking neural activity by tetrodotoxin disrupts the confined pattern of OPWs, resulting in a failure of transportation of inter-luminally injected ink. Finally, we have discovered a functional coupling of the endpoint of hindgut with the cloaca. When surgically separated, the cloaca ceases its acute contractions that would normally occur concomitantly with the peristaltic rhythm of the hindgut. Our findings shed light on the intrinsic regulations of gut peristalsis, including unprecedented ENS contribution and inter-region cross talk along the gut axis.

The gut contractile organoid: a novel model for studying the gut motility regulated by coordinating signals between interstitial cells of Cajal and smooth muscles

“…To understand the gut peristaltic movements, which reiterate at specific sites along the gut axis (Shikaya et al, 2022), deciphering the mechanisms underlying the coordination/synchronization of oscillators among multiple cells is critical. Exploiting the finding obtained in the current study that multiple organoids easily fuse each other in vitro, we have found that two organoids with different oscillatory rhythm eventually coordinate their phases upon the fusion (Fig.…”

“…Thus, it is tempting to speculate that during early gut peristalsis, ICCs might receive feedback from their governing SMCs to generate more stable coordination of pace-making activity among ICCs. Indeed, we have previously reported that in the very early embryonic gut, origins of peristaltic wave (OPW) are randomly distributed along the gut axis, but they later become confined to specific sites showing that ICCs undergo more stable and coordinated pace-making (Shikaya et al, 2022).…”

“…The embryonic gut therefore serves as a powerful model to study the intrinsic mechanisms underlying the peristalsis contrasting with the adult gut where ingested content influences the gut motility increasing complexity in analyses. We have recently reported using chicken embryos that sites of OPW are randomly distributed along the gut axis at early stages, and they later become confined to specific sites, and this confinement of OPWs enables rhythmic and patterned peristaltic movements (Shikaya et al, 2022). One of the long-standing and important questions is how the synchronized/coordinated contraction is achieved.…”