Postnatal growth in the intestine.

DOI:10.1097/MOG.0b013e32835d9ec3 Growth and development of the intestine in the postnatal period includes increases in crypt number, increases in intestinal length, the appearance of epithelial lineages [1], and changes in the absorptive functions of the epithelium [2]; however, in this review we will focus only on the expansion of crypt number and intestinal length. At birth, the rodent intestine has villi but no crypts; crypts develop in the first days of the postnatal period. Over the first 3 weeks of the postnatal life in the rodent there are increases in the number of crypts, number of cells per crypt, crypt height, villus height, the number of crypts per villus, the intestinal length, and the mucosal surface area [3,4]. The increase in crypt number is achieved by fission of existing crypts. Crypt fission is the symmetric longitudinal splitting of the crypt starting at the bottom near the muscularis mucosa and proceeding upwards [5]. In rodents, from 14 to 21 days of age, 25–35% of intestinal crypts are undergoing fission [4,6]. The percentage of crypts undergoing fission gradually decreases to a steady state of 5% in adult rodents. Humans have a similar surge in crypt fission but it occurs later at 6–9 months [7]. Crypt fission is preceded by an increase in the number of epithelial stem cells [8]. Two populations of intestinal epithelial stem cells have been identified [9,10]. An actively cycling population of crypt base columnar cells (CBCs), located between Paneth cells at the base of the crypts [11,12], and a quiescent population of stem cells at the þ4 position [13]. The two major pathways that influence proliferation and cytodifferentiation in the intestine are Wnt/ B-catenin and Notch. Proliferation of CBCs is controlled by the Wnt/B-catenin signaling pathway. In adults, CBCs are characterized by the expression of Lgr5, Ascl2, and Olfm4. Ascl2 controls stem cell number; increased Ascl2 expression results in increased proliferation, whereas deletion of Ascl2 blocks renewal of CBCs [14]. Lgr5 and Ascl2 are involved in WNT signaling, whereas Olfm4 is involved in Notch signaling. Crypt fission begins at the base of the crypt near the CBCs; whether CBCs participate in the initiation of crypt fission is unknown. In adults þ4 intestinal stem cells express Bmi1 and mouse telemorase reverse transcriptase (mTert). The stem cell markers that are coexpressed