Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States.
Department of Biology, University of Oregon, Eugene, Oregon, United States.
Am J Physiol Gastrointest Liver Physiol. 2023 Dec 1;325(6):G570-G581. doi: 10.1152/ajpgi.00094.2023. Epub 2023 Oct 24.
Growth and specification of the mouse intestine occurs in utero and concludes after birth. Although numerous studies have examined this developmental process in the small intestine, far less is known about the cellular and molecular cues required for colon development. In this study, we examine the morphological events leading to crypt formation, epithelial cell differentiation, proliferation, and the emergence and expression of a stem and progenitor cell marker Lrig1. Through multicolor lineage tracing, we show Lrig1-expressing cells are present at birth and behave as stem cells to establish clonal crypts within 3 wk of life. In addition, we use an inducible knockout mouse to eliminate and show restrains proliferation within a critical developmental time window, without impacting colonic epithelial cell differentiation. Our study illustrates morphological changes during crypt development and the importance of Lrig1 in the developing colon. Our studies define the importance of studying Lrig1 in colon development. We address a critical gap in the intestinal development literature and provide new information about the molecular cues that guide colon development. Using a novel, inducible knockout of , we show Lrig1 is required for appropriate colon epithelial growth and illustrate the importance of Lrig1-expressing cells in the establishment of colonic crypts.
小鼠肠道的生长和特化发生在子宫内,并在出生后结束。尽管许多研究已经检查了小肠的这个发育过程,但对于大肠发育所需的细胞和分子线索知之甚少。在这项研究中,我们检查了导致隐窝形成、上皮细胞分化、增殖以及出现和表达干细胞和祖细胞标记物 Lrig1 的形态事件。通过多色谱系追踪,我们发现在出生时就存在表达 Lrig1 的细胞,并且作为干细胞在生命的头 3 周内建立克隆隐窝。此外,我们使用诱导型敲除小鼠消除 ,并表明 在关键的发育时间窗口内限制增殖,而不影响结肠上皮细胞分化。我们的研究说明了隐窝发育过程中的形态变化以及 Lrig1 在发育中的结肠中的重要性。我们的研究阐明了研究 Lrig1 在结肠发育中的重要性。我们解决了肠道发育文献中的一个关键空白,并提供了有关指导结肠发育的分子线索的新信息。使用新型诱导型 的敲除,我们表明 Lrig1 是结肠上皮生长所必需的,并说明了表达 Lrig1 的细胞在结肠隐窝建立中的重要性。