PDF(Pubmed)
Abstract：
Correct intestinal morphogenesis depends on the early embryonic process of gut rotation, an evolutionarily conserved program in which a straight gut tube elongates and forms into its first loops. However, the gut tube requires guidance to loop in a reproducible manner. The dorsal mesentery (DM) connects the gut tube to the body and directs the lengthening gut into stereotypical loops via left-right (LR) asymmetric cellular and extracellular behavior. The LR asymmetry of the DM also governs blood and lymphatic vessel formation for the digestive tract, which is essential for prenatal organ development and postnatal vital functions including nutrient absorption. Although the genetic LR asymmetry of the DM has been extensively studied, a divider between the left and right DM has yet to be identified. Setting up LR asymmetry for the entire body requires a Lefty1+ midline barrier to separate the two sides of the embryo-without it, embryos have lethal or congenital LR patterning defects. Individual organs including the brain, heart, and gut also have LR asymmetry, and while the consequences of left and right signals mixing are severe or even lethal, organ-specific mechanisms for separating these signals are not well understood. Here, we uncover a midline structure composed of a transient double basement membrane, which separates the left and right halves of the embryonic chick DM during the establishment of intestinal and vascular asymmetries. Unlike other basement membranes of the DM, the midline is resistant to disruption by intercalation of Netrin4 (Ntn4). We propose that this atypical midline forms the boundary between left and right sides and functions as a barrier necessary to establish and protect organ asymmetry.
摘要：
正确的肠道形态发生取决于肠道旋转的早期胚胎过程，一种进化上保守的程序，其中直肠管伸长并形成其第一个环。然而,肠管需要引导以可重复的方式循环。背侧肠系膜（DM）将肠管连接到身体，并通过左右（LR）不对称的细胞和细胞外行为将延长的肠道引导到刻板的环中。DM的LR不对称性还控制消化道的血液和淋巴管形成。这对于产前器官发育和产后重要功能，包括营养吸收至关重要。虽然DM的遗传LR不对称性已被广泛研究，左DM和右DM之间的分隔物尚未被识别。为整个身体设置LR不对称性需要Lefty1+中线屏障来分隔胚胎的两侧-没有它，胚胎有致命或先天性LR模式缺陷。包括大脑在内的个体器官,心,肠道也有LR不对称性，虽然左右信号混合的后果是严重的，甚至是致命的，分离这些信号的器官特异性机制尚不清楚。这里,我们发现了一个由短暂的双基底膜组成的中线结构，在建立肠道和血管不对称的过程中，将胚胎小鸡DM的左右两部分分开。与DM的其他基底膜不同，中线对插入Netrin4（Ntn4）的破坏具有抵抗力。我们建议这种非典型的中线形成左右两侧之间的边界，并充当建立和保护器官不对称所必需的屏障。
