Intestinal cylindrical growth peaks in mice a few weeks after birth, simultaneously with
crypt fission activity. It nearly stops after weaning and cannot be reactivated later. Transgenic mice expressing Cd97/Adgre5 in the intestinal epithelium develop a mega-intestine with normal microscopic
morphology in adult mice. Here, we demonstrate premature intestinal differentiation in Cd97/Adgre5
transgenic mice at both the cellular and molecular levels until postnatal day 14. Subsequently, the
growth of the intestinal epithelium becomes activated and its maturation suppressed. These changes
are paralleled by postnatal regulation of growth factors and by an increased expression of secretory
cell markers, suggesting growth activation of non-epithelial tissue layers as the origin of enforced
tissue growth. To understand postnatal intestinal growth mechanistically, we study epithelial fate
decisions during this period with the use of a 3D individual cell-based computer model. In the model,
the expansion of the intestinal stem cell (SC) population, a prerequisite for crypt fission, is largely
independent of the tissue growth rate and is therefore not spontaneously adaptive. Accordingly,
the model suggests that, besides the growth activation of non-epithelial tissue layers, the formation
of a mega-intestine requires a released growth control in the epithelium, enabling accelerated SC
expansion. The similar intestinal morphology in Cd97/Adgre5 transgenic and wild type mice indicates a synchronization of tissue growth and SC expansion, likely by a crypt density-controlled
contact inhibition of growth of intestinal SC proliferation. The formation of a mega-intestine with
normal microscopic morphology turns out to originate in changes of autonomous and conditional
specification of the intestinal cell fate induced by the activation of Cd97/Adgre5.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:88568 |
| Date | 11 December 2023 |
| Creators | Hofmann, Felix, Thalheim, Torsten, Rother, Karen, Quaas, Marianne, Kerner, Christiane, Przybilla, Jens, Aust, Gabriela, Galle, Joerg |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1422-0067, 10.3390/ijms22147345 |
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