FGF8 coordinates tissue elongation and cell epithelialization during early kidney tubulogenesis.

胚成長と連動する管組織形成メカニズムの解明 －臓器不全治療や再生医療に期待－. 京都大学プレスリリース. 2015-07-03.When a tubular structure forms during early embryogenesis, tubular elongation and lumen formation (epithelialization) proceed simultaneously in a spatiotemporally coordinated manner. We here demonstrate, using the Wolffian duct (WD) of early chicken embryos, that this coordination is regulated by the expression of FGF8, which shifts posteriorly during body axis elongation. FGF8 acts as a chemoattractant on the leader cells of the elongating WD and prevents them from epithelialization, whereas static ('rear') cells that receive progressively less FGF8 undergo epithelialization to form a lumen. Thus, FGF8 acts as a binary switch that distinguishes tubular elongation from lumen formation. The posteriorly shifting FGF8 is also known to regulate somite segmentation, suggesting that multiple types of tissue morphogenesis are coordinately regulated by macroscopic changes in body growth

Early formation of the Mullerian duct is regulated by sequential actions of BMP/Pax2- and FGF/Lim1 signaling

The Müllerian duct (MD) and Wolffian duct (WD) are embryonic tubular tissues giving rise to female and male reproductive tracts, respectively. In amniote embryos, both MD and WD emerge in both sexes, but subsequently degenerate in the males and females, respectively. Here, by using MD-specific gene manipulations in chicken embryos, we identify the molecular and cellular mechanisms that link early MD specification to tubular invagination. Early (pre-)specification of MD precursors in the coelomic epithelium requires BMP signaling and its downstream target Pax2 in a WD-independent process. Subsequently, the BMP/Pax2 axis induces Lim1 expression, a hallmark of MD specification, for which FGF/ERK and WD-derived signals are also required. Finally, the sequential actions of the BMP/Pax2 and FGF/Lim1 axes culminate in epithelial invagination to form a tubular structure driven by an apical constriction, where apical accumulation of phospho-myosin light chain is positively regulated by FGF/ERK signaling. Our study delineates mechanisms governing the early formation of the MD, and also serves as a model of how an epithelial cell sheet is transformed to a tubular structure, a process seen in a variety of developmental contexts

神経性間欠跛行を再現するfictive実験モデル

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FLEXOR ACTIVITY BY INTRAMEDULLARY PRESSURE IN RABBIT FEMORAL BONE: An experimental study on thigh pain after total hip arthroplasty

雑誌掲載版Thigh pain often appears after total hip arthroplasty (THA) using a cementless femoral component. It is known that sensory nerve endings exist in the medullary cavity of the bone. The purpose of this study was to investigate, in a rabbit model, whether the pressure on the femoral bone applied from inside the medullary cavity of the femoral bone causes flexion withdrawal reflex. 　We loaded pressure on the inside of the medullary cavity of the femoral bone and observed whether muscle activity occurs. The pain resulting from pressure was evaluated by hind limb flexor activity produced by the flexor reflex. An integrated waveform was used to evaluate the degree of muscle activity. For the laboratory-animal models, we prepared the medullary cavity of the rabbits in two ways. In the rabbits with slight reaming, the flexor reflex appeared in low pressure. However, in rabbits with greater reaming, the flexor reflex did not appear, even under high pressure. This suggests that the pain was induced when the sensory nerve endings remained in the inside of the medullary cavity of the femoral bone and the sensory nerve endings were stimulated by the stress

System for Detecting Kindergartners

This paper describes a system for detecting kindergartner

【肩甲帯部痛の診療】 肩甲帯部痛をきたす頸椎疾患

雑誌掲載版肩甲帯部痛をきたす頸椎構成単位としては、椎間板・椎間関節・神経根が挙げられる。疼痛の起源が椎間板に存在する場合は洞脊椎神経を介して、椎間関節に存在する場合は頸神経根背側枝(内側枝)を介して、神経根にあった場合は頸神経根鞘に存在する自由神経終末を介して、求心性に侵害受容刺激を送る。このとき、これらの脊髄神経と同じまたは近接する高位のミオトーム領域に関連痛が投影されて、皮膚知覚と異なる、より深部に感じる鈍い・だるいような疼痛を肩甲帯部に自覚すると考えられる。頸椎運動で誘発される肩甲帯部痛では、頸椎疾患の存在を念頭に慎重な診察を行う必要がある。神経学的所見や画像所見を適切に評価し、手術適応のない症例では保存的治療として薬物療法・理学療法・注射療法などを用いて症状の軽減を図るべきである

Integration of Shh and Fgf signaling in controlling <i>Hox</i> gene expression in cultured limb cells

During embryonic development, fields of progenitor cells form complex structures through dynamic interactions with external signaling molecules. How complex signaling inputs are integrated to yield appropriate gene expression responses is poorly understood. In the early limb bud, for instance, Sonic hedgehog (Shh) is expressed in the distal posterior mesenchyme, where it acts as a mediator of anterior to posterior (AP) patterning, whereas fibroblast growth factor 8 (Fgf8) is produced by the apical ectodermal ridge (AER) at the distal tip of the limb bud to direct outgrowth along the proximal to distal (PD) axis. Here we use cultured limb mesenchyme cells to assess the response of the target Hoxd genes to these two factors. We find that they act synergistically and that both factors are required to activate Hoxd13 in limb mesenchymal cells. However, the analysis of the enhancer landscapes flanking the HoxD cluster reveals that the bimodal regulatory switch observed in vivo is only partially achieved under these in vitro conditions, suggesting an additional requirement for other factors

Differential modularity of the mammalian Engrailed 1 enhancer network directs sweat gland development.

Enhancers are context-specific regulators of expression that drive biological complexity and variation through the redeployment of conserved genes. An example of this is the enhancer-mediated control of Engrailed 1 (EN1), a pleiotropic gene whose expression is required for the formation of mammalian eccrine sweat glands. We previously identified the En1 candidate enhancer (ECE) 18 cis-regulatory element that has been highly and repeatedly derived on the human lineage to potentiate ectodermal EN1 and induce our species' uniquely high eccrine gland density. Intriguingly, ECE18 quantitative activity is negligible outside of primates and ECE18 is not required for En1 regulation and eccrine gland formation in mice, raising the possibility that distinct enhancers have evolved to modulate the same trait. Here we report the identification of the ECE20 enhancer and show it has conserved functionality in mouse and human developing skin ectoderm. Unlike ECE18, knock-out of ECE20 in mice reduces ectodermal En1 and eccrine gland number. Notably, we find ECE20, but not ECE18, is also required for En1 expression in the embryonic mouse brain, demonstrating that ECE20 is a pleiotropic En1 enhancer. Finally, that ECE18 deletion does not potentiate the eccrine phenotype of ECE20 knock-out mice supports the secondary incorporation of ECE18 into the regulation of this trait in primates. Our findings reveal that the mammalian En1 regulatory machinery diversified to incorporate both shared and lineage-restricted enhancers to regulate the same phenotype, and also have implications for understanding the forces that shape the robustness and evolvability of developmental traits

【腰痛症発生メカニズムと診断,治療】 腰痛症発生の病態 姿勢と腰痛

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