Histopathological evaluation of crypt fission during intestinal development          in neonatal mice

Yamazaki, Masaki; Fujii, Etsuko; Watanabe, Takeshi; Kato, Atsuhiko; Suzuki, Masami

doi:10.1293/tox.2019-0032

Cited by 8 publications

(7 citation statements)

References 18 publications

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“…Of note, in mice this process continues until 2 weeks after birth, while human intestinal development is completed before birth [ 38 ]. During this final maturation phase, intestinal elongation is further promoted by both crypt and villus fission events [ 34 , 39 – 41 ]. Although the frequency of crypt fission events is higher during development, this process still occurs at low frequency in the adult epithelium as well [ 39 , 42 ].…”

Section: Intestinal Developmentmentioning

confidence: 99%

“…These features of crypt development are also observed in maturing organoids [ 46 , 66 ]. Strikingly, mature Paneth cells only appear 2 weeks after birth when crypt development is finalized [ 39 , 67 – 69 ]. This comprises the last step in the maturation process to establish a homeostatic self-renewing intestinal epithelium.…”

Section: Intestinal Developmentmentioning

confidence: 99%

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Organoid-based modeling of intestinal development, regeneration, and repair

2020

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The intestinal epithelium harbors a remarkable adaptability to undergo injury-induced repair. A key part of the regenerative response is the transient reprogramming of epithelial cells into a fetal-like state, which drives uniform proliferation, tissue remodeling, and subsequent restoration of the homeostatic state. In this review, we discuss how Wnt and YAP signaling pathways control the intestinal repair response and the transitioning of cell states, in comparison with the process of intestinal development. Furthermore, we highlight how organoid-based applications have contributed to the characterization of the mechanistic principles and key players that guide these developmental and regenerative events.

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Section: Intestinal Developmentmentioning

confidence: 99%

Section: Intestinal Developmentmentioning

confidence: 99%

Organoid-based modeling of intestinal development, regeneration, and repair

2020

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“…Afterwards, crypts reach a size where they start fission (Video A). Fission is induced by separating PC clusters and includes fibroblast movement similar to that of mice [ 40 , 41 ]. Most of the crypt fission events take place within cross-sections of the cylinder as crypts expand asymmetrically due to radial growth ( Figure 7 A).…”

Section: Resultsmentioning

confidence: 99%

How to Obtain a Mega-Intestine with Normal Morphology: In Silico Modelling of Postnatal Intestinal Growth in a Cd97-Transgenic Mouse

Hofmann

Thalheim

Rother

et al. 2021

IJMS

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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.

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“…The renewal of the colon epithelial cell occurs rapidly and continuously within the crypt, however under normal homeostatic conditions, crypt production is a rare event: less than 1 in 200 crypts in the mouse colon are in the process of budding 2,40 and in the normal human colon less than 1 in 2000 crypts are producing crypt buds 41 . During development 42 , intestinal renewal after physical 272 damage, radiation, infection and adenoma formation, crypt budding occurs 273 frequently 43 . In normal tissue, once homeostasis is achieved, crypt budding ceases.…”

Section: Discussionmentioning

confidence: 99%

ErbB Receptor Stimulation Is Required for Mouse Colon Adenoma Organoids to Form Crypts

Tan

Zhu

Kane

et al. 2021

Preprint

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The majority of colon adenomas harbor genetic mutations in the APC gene. APC mutation leads to changes in Wnt signalling and cell-cell adhesion: as a consequence, intestinal crypt budding increases and the excess crypts accumulate to form adenomas that progress to colon cancer. When cultured with Wnt, R-spondin, EGF, Noggin, myofibroblast conditioned medium and Matrigel, crypts from normal mouse colon mucosa form crypt-producing organoids and can be passaged continuously. Under the same culture and passage conditions, crypts isolated from colon adenomas derived from Apcmin/+ mice typically grow as spheroidal cysts and do not produce crypts. The adenoma organoid growth requires EGF, but not Wnt, R-spondin or Noggin. However, when mouse colon adenoma spheroids are grown for more than 10 days in the presence of EGF, crypt formation occurs. EGF, EREG, β-cellulin, Neuregulin-1 or AREG are sufficient for initiating crypt formation, however, neuregulin-1 is more potent than the other EGF-family members. EGFR and ErbB2 inhibitors both prevent crypt formation in adenoma cultures. Either EGFR:ErbB2 or ErbB3:ErbB2 signalling is sufficient to initiate adenoma crypt budding and elongation. ErbB2 inhibitors may provide a therapeutic avenue for controlling and ablating colon adenomas.

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Histopathological evaluation of crypt fission during intestinal development in neonatal mice

Cited by 8 publications

References 18 publications

Organoid-based modeling of intestinal development, regeneration, and repair

Organoid-based modeling of intestinal development, regeneration, and repair

How to Obtain a Mega-Intestine with Normal Morphology: In Silico Modelling of Postnatal Intestinal Growth in a Cd97-Transgenic Mouse

ErbB Receptor Stimulation Is Required for Mouse Colon Adenoma Organoids to Form Crypts

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