Reelin Is Involved in the Crypt-Villus Unit Homeostasis

Abstract

Intestinal myofibroblasts secrete substances that control organogenesis and wound repair of the intestine. The myofibroblasts of the rat small intestine express reelin and the present work explores whether reelin regulates crypt-villus unit homeostasis using normal mice and mice with the reelin gene disrupted (reeler). The results reveal that mouse small intestine expresses reelin, its receptors apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor (VldlR) and the reelin effector protein Disabled-1 (Dab1) and that reelin expression is restricted to myofibroblasts. The absence of reelin significantly reduces epithelial cell proliferation, migration, and apoptosis and the number of Paneth cells. These effects are observed during the suckling, weaning, and adult periods. The number of Goblet cells is increased in the 2-month-old reeler mice. The absence of reelin also expands the extracellular space of the adherens junctions and desmosomes without significantly affecting either the tight-junction structure or the epithelial paracellular permeability. In conclusion, this is the first in vivo work showing that the absence of reelin alters intestinal epithelium homeostasis.

Small intestinal stem cells

“…We know that the underlying mesenchyme plays a role in the development of the intestinal epithelium and that factors such as epimorphin, Wnt2b, Bmp4, reelin, and other growth factors influence ISC function [41][42][43][44]. Recently, Neal et al [45] provided evidence suggesting that ISCs express TLR4 and that activation of TLR4 by bacterial products controls the ability of ISCs to proliferate and undergo apoptosis.…”

Reelin‐Dab1 signaling system in human colorectal cancer

“…In brain the reelin signaling system is essential for proper positioning of migrating neurons during the development of the central nervous system [1], but its role in peripheral tissues is not well understood. We have previously reported that rat small intestine expresses reelin, its receptors VLDLR (very low density-lipoprotein receptor) and ApoER2 (apolipoprotein E receptor 2), and its cytosolic effector protein Dab1 (Disabled-1) [2] and that reelin deficiency alters the balance between cell proliferation, differentiation, and apoptosis of the crypt-villus unit in mice [3]. As reelin mRNA and protein expression is restricted to the subepithelial myofibroblasts and the other components of the signaling system are localized to the epithelium cells and myofibroblasts [2], we suggested that the reelin released to the extracellular matrix by the myofibroblasts might act on the epithelial cells and regulate the dynamics of the crypt-villus unit.…”

Interdigital cell death in the embryonic limb is associated with depletion of Reelin in the extracellular matrix

“…42, 43, 44, 45, 46 Our findings suggest that Reelin contributes to the creation of an extracellular substrate required for maintaining the viability of undifferentiated limb mesodermal cells until they initiate differentiation. In chick limbs, the interdigital expression of reelin is intensely downregulated preceding cell death.…”