I outline here the development of intestinal motility in the chicken embryo. The first contractile events are circular smooth muscle driven calcium waves (E6), that gain a clock-like regularity when ...interstitial cells of Cajal become electrically active (E14). Soon after longitudinal smooth muscle contractions become prominent (E14), the enteric nervous system starts controlling motility (E16) by coupling the longitudinal and circular contractions via inhibitory neurotransmission. It gives rise to circular-longitudinal antagonism, to the migrating motor complex, and to the polarized ascending contraction-descending relaxation pressure response known as the "law of the intestine". The kinetics of gut development in the chicken appears to follow faithfully that of humans by simply converting embryonic days of chicken development into embryonic weeks of human development.
Peristalsis enables transport of the food bolus in the gut. Here, I show by dynamic ex vivo intra-cellular calcium imaging on living embryonic gut explants that the most primitive form of peristalsis ...that occurs in the embryo is the result of inter-cellular, gap-junction-dependent calcium waves that propagate in the circular smooth muscle layer. I show that the embryonic gut is an intrinsically mechanosensitive organ, as the slightest externally applied mechanical stimulus triggers contractile waves. This dynamic response is an embryonic precursor of the ‘law of the intestine’ (peristaltic reflex). I show how characteristic features of early peristalsis such as counter-propagating wave annihilation, mechanosensitivity and nucleation after wounding all result from known properties of calcium waves. I finally demonstrate that inter-cellular mechanical tension does not play a role in the propagation mechanism of gut contractile waves, unlike what has been recently shown for the embryonic heartbeat. Calcium waves are a ubiquitous dynamic signalling mechanism in biology: here I show that they are the foundation of digestive movements in the developing embryo.
This article is part of the Theo Murphy meeting issue on ‘Mechanics of development’.
Young children engage cognitive control reactively in response to events, rather than proactively preparing for events. Such limitations in executive control have been explained in terms of ...fundamental constraints on children's cognitive capacities. Alternatively, young children might be capable of proactive control but differ from older children in their metacognitive decisions regarding when to engage proactive control. We examined these possibilities in three conditions of a task-switching paradigm, varying in whether task cues were available before or after target onset. RTs, ERPs, and pupil dilation showed that 5-year-olds did engage in advance preparation, a critical aspect of proactive control, but only when reactive control was made more difficult, whereas 10-year-olds engaged in proactive control whenever possible. These findings highlight metacognitive processes in children's cognitive control, an understudied aspect of executive control development.
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.
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.
We study the effect of wetting properties on the propensity of a surface to heterogeneously nucleate or adsorb calcium carbonate from a saturated aqueous solution. Glass, silanized glass, and ...polyethylene surfaces are considered. UV-ozone is used to tune the wetting behavior from hydrophobic to hydrophilic by forming oxidized carbon groups (alcohol, aldehyde, carboxylic). For all substrates that do not promote any specific orientation of CaCO3 crystals, increasing hydrophilicity inhibits CaCO3 nucleation. Complete ⟨104⟩ and ⟨001⟩ crystal orientations relative to the substrate plane are obtained for silanized glass exposed to prolonged UV-ozone treatment; nucleation densities are then also considerably higher. Our results highlight the role of interfacial surface energies and orientation in heterogeneous crystal nucleation and adsorption phenomena and contribute to the rational design of antiscaling surface treatments.
Embryogenesis of the peristaltic reflex Chevalier, Nicolas R.; Dacher, Nicolas; Jacques, Cécile ...
Journal of physiology,
05/2019, Letnik:
597, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Key points
Neurogenic gut movements start after longitudinal smooth muscle differentiation in three species (mouse, zebrafish, chicken), and at E16 in the chicken embryo.
The first activity of the ...chicken enteric nervous system is dominated by inhibitory neurons.
The embryonic enteric nervous system electromechanically couples circular and longitudinal spontaneous myogenic contractions, thereby producing a new, rostro‐caudally directed bolus transport pattern: the migrating motor complex.
The response of the embryonic gut to mechanical stimulation evolves from a symmetric, myogenic response at E12, to a neurally mediated, polarized, descending inhibitory, ‘law of the intestine’‐like response at E16.
High resolution, whole‐mount 3D reconstructions are presented of the enteric nervous system of the chicken embryo at the neural‐control stage E16 with the iDISCO+ tissue clarification technique.
Gut motility is a complex transport phenomenon involving smooth muscle, enteric neurons, glia and interstitial cells of Cajal. Because these different cells differentiate and become active at different times during embryo development, studying the ontogenesis of motility offers a unique opportunity to ‘time‐reverse‐engineer’ the peristaltic reflex. Working on chicken embryo intestinal explants in vitro, we found by spatio‐temporal mapping and signal processing of diameter and position changes that motility follows a characteristic sequence of increasing complexity: (1) myogenic circular smooth muscle contractions from E6 to E12 that propagate as waves along the intestine, (2) overlapping and independent, myogenic, low‐frequency, bulk longitudinal smooth muscle contractions around E14, and (3) tetrodotoxin‐sensitive coupling of longitudinal and circular contractions by the enteric nervous system as from E16. Inhibition of nitric oxide synthase neurons shows that the coupling consists in nitric oxide‐mediated relaxation of circular smooth muscle when the longitudinal muscle layer is contracted. This mechanosensitive coupling gives rise to a directional, cyclical, propagating bolus transport pattern: the migrating motor complex. We further reveal a transition to a polarized, descending, inhibitory reflex response to mechanical stimulation after neuronal activity sets in at E16. This asymmetric response is the elementary mechanism responsible for peristaltic transport. We finally present unique high‐resolution 3D reconstructions of the chicken enteric nervous system at the neural‐control stage based on confocal imaging of iDISCO+ clarified tissues. Our study shows that the enteric nervous system gives rise to new peristaltic transport patterns during development by coupling spontaneous circular and longitudinal smooth muscle contraction waves.
Key points
Neurogenic gut movements start after longitudinal smooth muscle differentiation in three species (mouse, zebrafish, chicken), and at E16 in the chicken embryo.
The first activity of the chicken enteric nervous system is dominated by inhibitory neurons.
The embryonic enteric nervous system electromechanically couples circular and longitudinal spontaneous myogenic contractions, thereby producing a new, rostro‐caudally directed bolus transport pattern: the migrating motor complex.
The response of the embryonic gut to mechanical stimulation evolves from a symmetric, myogenic response at E12, to a neurally mediated, polarized, descending inhibitory, ‘law of the intestine’‐like response at E16.
High resolution, whole‐mount 3D reconstructions are presented of the enteric nervous system of the chicken embryo at the neural‐control stage E16 with the iDISCO+ tissue clarification technique.
The intestine is the most anisotropically shaped organ, but, when grown in culture, embryonic intestinal stem cells form star- or sphere-shaped organoids. Here, we present evidence that spontaneous ...tonic and phasic contractions of the circular smooth muscle of the embryonic gut cause short-timescale elongation of the organ by a purely mechanical, self-squeezing effect. We present an innovative culture set-up to achieve embryonic gut growth in culture and demonstrate by three different methods (embryological, pharmacological and microsurgical) that gut elongational growth is compromised when smooth muscle contractions are inhibited. We conclude that the cumulated short-term mechanical deformations induced by circular smooth muscle lead to long-term anisotropic growth of the gut, thus demonstrating a self-consistent way by which the function of this organ (peristalsis) directs its shape (morphogenesis). Our model correctly predicts that longitudinal smooth muscle differentiation later in embryogenesis slows down elongation, and that several mice models with defective gut smooth muscle contractility also exhibit gut growth defects. We lay out a comprehensive scheme of forces acting on the gut during embryogenesis and of their role in the morphogenesis of this organ. This knowledge will help design efficient
organ growth protocols and handle gut growth pathologies such as short bowel syndrome.
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