Lrig1 drives cryptogenesis and restrains proliferation during colon development.

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 Lrig1 and show Lrig1 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.NEW & NOTEWORTHY 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 Lrig1, we show Lrig1 is required for appropriate colon epithelial growth and illustrate the importance of Lrig1-expressing cells in the establishment of colonic crypts.

The Role of Lrig1 in the Development of the Colonic Epithelium.

Growth and specification of the mouse intestine occurs in utero and concludes after birth. While 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, areas of 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 three weeks after birth. In addition, we use an inducible knockout mouse to eliminate Lrig1 during colon development and show loss of Lrig1 restrains proliferation within a critical developmental time window, without impacting colonic epithelial cell differentiation. Our study illustrates the morphological changes that occur during crypt development and the importance of Lrig1 in the developing colon.