京都大学 大学院医学研究科 人間健康科学系専攻 病理学研究室（形態形成医療科学）

野原さんの修論がJ Anatomyに掲載されました。

胚子期末の２次口蓋形成時の舌、口蓋だな、下顎（メッケル軟骨）、鼻腔の動きを主成分分析等を用いて解析し、口蓋だな上昇、融合前の数日間の下顎（メッケル軟骨）、舌が極度に前後に圧縮される時期を”approach period”として見出しました。

• 口蓋棚の上昇・癒合はCS23中におきる。
• 「アプローチ期間」の間、下顎骨 (メッケル軟骨と舌) と上顎骨 (口蓋と鼻腔) の構造は位置を変えなかったが、構造の両方のグループが前後に圧縮されていた。
• 口蓋棚上昇前後では、上顎と下顎の構造、特に舌の上の棚の配置、および舌と下顎骨の突出の間に有意な変化を示した。
• これらの結果は、メッケル軟骨の成長が舌を再配置して棚の上昇を促進する上で積極的な役割を果たしていることを示唆している。

ヒトの二次口蓋閉鎖の 3 つの異なるPhaseを表す現在のデータは、口蓋棚の水平配置の前後に発生する形態学的成長変化と、ヒトの二次口蓋をうまく閉じるためのそれらの融合の理解を進めることができます。

 Nohara A, Owaki N, Matsubayashi J, Katsube M, Imai H, Yoneyama A, Yamada S, Kanahashi T, Takakuwa T. Morphometric analysis of secondary palate development in human embryos. J Anatomy, 2022, 241(6), 1287-1302, 2022, DOI:10.1111/joa.13745

Abstract

Rapid shelf elevation and contact of the secondary palate and fusion reportedly occur due to a growth-related equilibrium change in the structures within the oro-nasal cavity. This study aimed to quantitatively evaluate complex three-dimensional morphological changes and their effects on rapid movements, such as shelf elevation and contact, and fusion. Morphological changes during secondary palate formation were analyzed using high-resolution digitalized imaging data (phase-contrast X-ray computed tomography and magnetic resonance images) obtained from 22 human embryonic and fetal samples. The three-dimensional images of the oro-nasal structures, including the maxilla, palate, pterygoid hamulus, tongue, Meckel’s cartilage, nasal cavity, pharyngeal cavity, and nasal septum, were reconstructed manually.

palatal shelves were not elevated in all the samples at Carnegie stage (CS)21 and CS22 and in three samples at CS23. In contrast, the palatal shelves were elevated but not in contact in one sample at CS23. Further, the palatal shelves were elevated and fused in the remaining four samples at CS23 and all three samples from the early fetal period. For each sample, 70 landmarks were subjected to Procrustes and principal component (PC) analysis. PC-1 accounted for 67.4% of the extracted gross changes before and after shelf elevations. Notably, the PC-1 values of the negative and positive value groups differed significantly. The PC-2 value changed during the phases in which the change in the PC-1 value was unnaturally slow and stopped at CS22 and the first half of CS23. This period, defined as the “approach period”, corresponds to the time before dynamic changes occur as the palatal shelves elevate, the tongue and mandibular tip change their position and shape, and secondary palatal shelves contact and fuse. During the “approach period”, measurements of PC-2 changes showed that structures on the mandible (Meckel’s cartilage and tongue) and maxilla (palate and nasal cavity) did not change positions, albeit both groups of structures appeared to be compressed anterior-posteriorly. However, during and after shelf elevation, measurements of PC-1 changes showed significant changes between maxillary and mandibular structures, particularly positioning of the shelves above the tongue and protrusion of the tongue and mandible. These results suggest an active role for Meckel’s cartilage growth in repositioning the tongue to facilitate shelf elevation. The present data representing three distinct phases of secondary palate closure in humans can advance the understanding of morphological growth changes occurring before and after the horizontal positioning of palatal shelves and their fusion to close the secondary palate in humans successfully.

石川さんが、第9回 International Symposium on Regenerative Rehabilitationで発表しました(2022年10月27-29日)

Ishikawa A, Nagai-Tanima M, Ishida K, Imai H, Yamada S, Aoyama T, Takakuwa T.  Three-dimensional morphological comparison of the knee at different stages of normal human development. the 9th Annual International Symposium on Regenerative Rehabilitation 2022年10月27-29日、於：Austin,TEXAS.

掛谷さんの修士論文がJ Anatomyに掲載されました。

発生途中、消化管は臍帯腔内に脱出し、CRL40mmころに短時間で還納されます。還納の仕方は、これまで消化管の動きを中心に研究されており、slide-stack model（消化管はループを形成したまま還納するというモデル）が優勢でした。本論文では、下記の２つの定説を覆す内容です。

• 消化管の臍帯内脱出の還納はCRL30mmころから時間をかけて行われること
• 消化管は臍帯輪通過時にはループが解除されていること

複雑な小腸の走行を追跡しても限界があることを認識し、この論文では消化管を栄養する上腸間膜動脈とその小腸枝の走行を正確に追うことで、還納経過中の小腸の位置や形状、走行をしめすとともに、血管系の分布、形状変化も示すことができました。還納は腸管の動きとして認識される時期に先行する血管系の位置の変化により開始され、これまでのコンセンサスよりも早く始まることを示しました。臍帯輪通過時には、消化管とそれを栄養する動脈の走行は形状を変えます。消化管はループがほどけ、臍帯輪を２本以上の消化管が通過することはありません。また、臍帯輪において消化管、腸間膜、動脈は整然とならび、どの個体でもほぼ一定です。

この組織だった配置は腸管への血行が安全に確保されるために必要とかんがえられます。

KakeyaM, Matsubayashi J, Kanahashi T, Männer J, Yamada S, Takakuwa T. The return process of physiological umbilical herniation in human fetuses: the possible role of the vascular tree and umbilical ring. J Anatomy 2022, 241(3), 846-859. https://doi.org/10.1111/joa.13720

Abstract

The human intestine elongates during the early fetal period, herniates into the extraembryonic coelom (EC), and subsequently returns to the abdominal cavity (AC). The process by which the intestinal loop returns to the abdomen remains unclear. This study aimed to document positional changes in the intestinal tract with the superior mesenteric artery (SMA) and branches in 3D to elucidate the intestinal loop return process (transition phase). Serial histological cross-sections from human fetuses (crown–rump length [CRL] range: 30–50 mm) in the herniation (n = 1), transition (n = 7), and return (n = 2) phases were selected from the Blechschmidt Collection. The distribution of the SMA trunk and all intestinal and sister branches entering the intestines was visualized so that positional changes in branches were continuous from the herniation to return phases. Positional changes in SMA branches proceeded in an orderly and structured manner; this is essential for continuous blood supply via the SMA to the intestine during transition and for safe intestinal return. Changes in the SMA distribution proceeded prior to the detection of initiation of intestinal tract return, which might start earlier and last much longer than our consensus (i.e., that the return of the herniated intestine begins when the CRL is approximately 40 mm and ends within a short time). In the cross-section of the umbilical ring in the herniation and transition phases, one proximal limb and one distal limb were observed with SMA intestinal branches, which were fully packed in the umbilical ring. The SMA branches were aligned from inferior to superior along the SMA main trunk. In the herniation phase, the distribution of 3rd–13th branches aligned from proximal inferior medial to distal superior left with a slight spiral in the EC, the tips of which suggested an orderly running course of the small intestine. In the transition phase, SMA branches running across the umbilical ring that fed the small intestine were observed, suggesting that the intestine was uncoiled and ran across the umbilical ring almost vertically. The estimated curvature value supported the phenomenon of uncoiling at the umbilical ring; the value at the umbilical ring was lesser than that in the AC and EC. During the transition phase, the proximal and distal limbs transversely ran side by side in the AC, umbilical ring, limbs on the cranial side, and mesentery on the caudal side. The SMA trunk and its branches ran in parallel, cranially to caudally aligned in the mesentery. This layout of the umbilical ring was maintained during the transition phase. In the return phase, the SMA trunk was gently curved from the upper left to the lower right of the AC; around 12 branches spread with a winding staircase appearance. The intestinal tract reached its definitive position immediately after all tissues crossed the umbilical ring and released any restriction. Each SMA branch and the corresponding region of the intestinal tract form a unit and change their position, though the conformation may change within each unit when running across the umbilical ring. We suggest that the slide–stack model requires revision.

第62回日本先天異常学会で発表しました(‘22,7/29-31, 金沢）

酷暑の中、対面、遠隔のハイブリッドで開催されました。

シンポジウム（正常と異常を顕かにするイメージング技術）

高桑徹也；三次元デジタル情報を活用したヒト胚子・胎児の解析
Analysis of human embryos and fetuses using three-dimensional digitalized images

＠座長もさせていただきました。現地に出席の方も結構おられ、かなり盛況でした。

一般演題

藤井 瀬菜、村中 太河、松林 潤、米山 明男、兵藤 一行、山田 重人、高桑徹也; ヒト胚子期における気管支樹の三次元的変化の定量的検討
The quantitative analysis of morphological change of the human embrionic bronchial tree

金橋　徹、今井宏彦、大谷　浩、山田重人、米山明男、高桑徹也; 拡散テンソルイメージングを応用したヒト胎児横隔膜形成の三次元的解析
Three-dimensional morphogenesis of the human diaphragm during the late embryonic and early fetal period: Analysis using diffusion tensor imaging