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The Primary Cilium on Cells of Developing Skeletal Rudiments; Distribution, Characteristics and Response to Mechanical Stimulation.

ABSTRACT: Embryo movement is important for tissue differentiation and the formation of functional skeletal elements during embryonic development: reduced mechanical stimulation results in fused joints and misshapen skeletal rudiments with concomitant changes in the signaling environment and gene expression profiles in both mouse and chick immobile embryos. Despite the clear relationship between movement and skeletogenesis, the precise mechanisms by which mechanical stimuli influence gene regulatory processes are not clear. The primary cilium enables cells to sense mechanical stimuli in the cellular environment, playing a crucial mechanosensory role during kidney development and in articular cartilage and bone but little is known about cilia on developing skeletal tissues. Here, we examine the occurrence, length, position, and orientation of primary cilia across developing skeletal rudiments in mouse embryos during a period of pronounced mechanosensitivity and we report differences and similarities between wildtype and muscle-less mutant (Pax3 ^Spd/Spd ) rudiments. Strikingly, joint regions tend to have cilia positioned and oriented away from the joint, while there was a less obvious, but still significant, preferred position on the posterior aspect of cells within the proliferative and hypertrophic zones. Regions of the developing rudiments have characteristic proportions of ciliated cells, with more cilia in the resting and joint zones. Comparing wildtype to muscle-less mutant embryos, cilia are shorter in the mutant with no significant difference in the proportion of ciliated cells. Cilia at the mutant joint were also oriented away from the joint line.

SUBMITTER: Shea CA

PROVIDER: S-EPMC8418538 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Stimulation of mechanoreceptors in skeletal muscles such as contraction and stretch elicits reflexive autonomic nervous system changes which impact cardiovascular control. There are pressure-sensitive mechanoreceptors in skeletal muscles. Mechanical pressure stimulation of skeletal muscles can induce reflex changes in heart rate (HR) and blood pressure, although the neural mechanisms underlying this effect are unclear. We examined the contribution of cardiac autonomic nerves to HR responses induced by mechanical pressure stimulation (30 s, ~10 N/cm2) of calf muscles in isoflurane-anesthetized rats. Animals were artificially ventilated and kept warm using a heating pad and lamp, and respiration and core body temperature were maintained within physiological ranges. Mechanical stimulation was applied using a stimulation probe 6 mm in diameter with a flat surface. Cardiac sympathetic and vagus nerves were blocked to test the contribution of the autonomic nerves. For sympathetic nerve block, bilateral stellate ganglia, and cervical sympathetic nerves were surgically sectioned, and for vagus nerve block, the nerve was bilaterally severed. In addition, mass discharges of cardiac sympathetic efferent nerve were electrophysiologically recorded. Mechanical stimulation increased or decreased HR in autonomic nerve-intact rats (range: -56 to +10 bpm), and the responses were negatively correlated with pre-stimulus HR (r = -0.65, p = 0.001). Stimulation-induced HR responses were markedly attenuated by blocking the cardiac sympathetic nerve (range: -9 to +3 bpm, p < 0.0001) but not the vagus nerve (range: -75 to +30 bpm, p = 0.17). In the experiments with cardiac sympathetic efferent nerve activity recordings, mechanical stimulation increased, or decreased the frequency of sympathetic nerve activity in parallel with HR (r = 0.77, p = 0.0004). Furthermore, the changes in sympathetic nerve activity were negatively correlated with its tonic level (r = -0.62, p = 0.0066). These results suggest that cardiac sympathetic nerve activity regulates HR responses to muscle mechanical pressure stimulation and the direction of HR responses depends on the tonic level of the nerve activity, i.e., bradycardia occurs when the tonic activity is high and tachycardia occurs when the activity is low.

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The Primary Cilium on Cells of Developing Skeletal Rudiments; Distribution, Characteristics and Response to Mechanical Stimulation.

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