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Tsujikawa, K.

Publications and source records attributed to Tsujikawa, K..

4 recordsLinked to original sources

Inward thickening of embryonic neuron-packing brain walls: Mechanical integrity via curvature-associated inner-surface contractility

Despite recent explorations of tissue-level epithelial morphogenesis, how the embryonic brain wall, an epithelial derivative unique in its extensive cellular stratification coupled with epithelial-cell heightening to [~]0.5 mm, achieves thickening is unknown. Furthermore, the role of the inner curvature of the wall in this process remains unclear. Thus, whether the apically concave dorsal cerebral (pallial) wall thickens inward, not only outward as previously thought, was examined in culture and in vivo. The pallial wall in the midembryonic period, but not the earlier pallial wall, thickened inward at a pace equivalent to that of neuronal accumulation, which was found via stress-release tests to proceed in a compressive manner. The inhibition of actomyosin-mediated contraction of the inner/apical surface prevented the pallium from thickening, while inducing apical-surface buckling, suggesting the necessity of this inward thickening to actively avoid overcrowding. In contrast, inward bulging of the apically convex ganglionic eminence occurs more passively via pushing of the low-actomyosin apical surface by the constituent cells.

developmental biology↗

CSF pressure in fetal mice in utero: External factors pressurize the intraventricular space

Previous experiments inducing leakage of embryonic cerebrospinal fluid (CSF) suggest the necessity of intraventricular CSF pressure (PCSF) for brain morphogenesis. Nevertheless, how embryonic PCSF occurs is unclear, especially in utero. Using a Landis water manometer, we measured PCSF in fetal mice isolated from the amniotic cavity (PCSF-ISO). At embryonic day (E) 13, PCSF-ISO was 82.7 Pa. Intraventricular injections of [≥]2 l of saline elevated PCSF-ISO by [~]30%. Intraventricularly injecting inhibitors of CSF secretion decreased PCSF-ISO by [~]30%. Shh-mediated cerebral-wall expansion and the resulting ventricular narrowing did not significantly increase PCSF-ISO. Removal of the brain-surrounding contractile tissues decreased PCSF-ISO by 80-90%. The intraamniotic pressure measured in utero (PAF-IU) was 1030.7 Pa. Our direct measurement revealed that the PCSF in utero (PCSF-IU) was 1076.4 Pa, confirming the susceptibility of PCSF to external factors. Subsequent PCSF measurements under hydrostatic pressure loading suggested that PCSF-IU = PCSF-ISO + PAF-IU, a relationship further used to estimate PCSF-IU at other ages when direct measurement was not possible. The estimated PCSF-IU decreased almost constantly from E10 to E16 (2000 500 Pa).

developmental biology↗

Mechanical collaboration between the embryonic brain and the surrounding scalp tissues

During brain enlargement between embryonic day (E) 11 and E13, within the limited mouse cranial space enclosed by the scalp consisting of epidermal and preosteogenic mesenchymal layers, the angle between the pons and the medulla decreases. This raises the possibility that the scalp, upon being pushed outwardly by the brain and stretched, in return inwardly recoils to confine and fold the brain. Our stress-releasing tests showed that the scalp recoiled to shrink more extensively at E12~13 than at E15~16 and that the in vivo pre-stretch prerequisite for this recoil response depended physically on the brain (pressurization at 77~93 Pa) and on actomyosin and elastin within the scalp layers. Under non-stretched conditions, scalp cell proliferation declined, while re-stretching of the shrunken scalp rescued proliferation. In scalp-removed heads, pons-medulla folding was reduced, and the spreading of ink from the lateral ventricle to the spinal cord that occurred in scalp-intact embryos (with >5 l injection) was lost, suggesting that the scalp plays roles in brain morphogenesis and cerebrospinal fluid homeostasis. Thus, the brain and the scalp mechanically interact and collaborate.

developmental biology↗

RAMP1 in Kupffer cells is a critical regulator in immune-mediated hepatitis

The significanceF of the relationship between the nervous and immune systems with respect to disease course is increasingly apparent. Immune cells in the liver and spleen are responsible for the development of acute liver injury, yet the regulatory mechanisms of the interactions remain elusive. Calcitonin gene-related peptide (CGRP), which is released from the sensory nervous system, regulates innate immune activation via receptor activity-modifying protein 1 (RAMP1), a subunit of the CGRP receptor. Here, we show that RAMP1 in Kupffer cells (KCs) plays a critical role in the etiology of immune-mediated hepatitis. RAMP1-deficient mice with concanavalin A (ConA)-mediated hepatitis, characterized by severe liver injury accompanied by infiltration of immune cells and increased secretion of pro-inflammatory cytokines by KCs and splenic T cells, showed poor survival. Removing KCs ameliorated liver damage, while depleting T cells or splenectomy led to partial amelioration. Adoptive transfer of splenic T cells from RAMP1-deficient mice led to a modest increase in liver injury. Co-culture of KCs with splenic T cells led to increased cytokine expression by both cells in a RAMP1-dependent manner. Thus, immune-mediated hepatitis develops via crosstalk between immune cells. RAMP1 in KCs is a key regulator of immune responses.

immunology↗