Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27Kip1 and p57Kip2.

O. Riccio; M.E. van Gijn; A.C. Bezdek; L. Pellegrinet; J.H. van Es; U. Zimber-Strobl; L.J. Strobl; T. Honjo; H. Clevers; F. Radtke

doi:10.1038/embor.2008.7

Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27Kip1 and p57Kip2.

O. Riccio, M.E. van Gijn, A.C. Bezdek, L. Pellegrinet, J.H. van Es, U. Zimber-Strobl, L.J. Strobl, T. Honjo, H. Clevers, F. Radtke

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

334 Citaten (Scopus)

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The crucial role of individual Notch receptors and the mechanism by which they maintain intestinal crypt progenitor cells were assessed by using a series of inducible gut-specific Notch mutant mice. We found that Notch1 and Notch2 receptors function redundantly in the gut, as only simultaneous loss of both receptors results in complete conversion of proliferating crypt progenitors into post-mitotic goblet cells. This conversion correlates with the loss of Hes1 expression and derepression of the cyclin-dependent kinase (CDK) inhibitors p27Kip1 and p57Kip2. We also found that the promoter of both CDK inhibitor genes is occupied by the Notch effector Hes1 in wild-type crypt progenitor cells. Thus, our results indicate that Notch-mediated Hes1 expression contributes to the maintenance of the proliferative crypt compartment of the small intestine by transcriptionally repressing two CDK inhibitors.

Originele taal-2	Engels
Pagina's (van-tot)	377-383
Tijdschrift	EMBO Reports
Volume	9
Nummer van het tijdschrift	4
DOI's	https://doi.org/10.1038/embor.2008.7
Status	Gepubliceerd - 2008

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10.1038/embor.2008.7

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Riccio, O., van Gijn, M. E., Bezdek, A. C., Pellegrinet, L., van Es, J. H., Zimber-Strobl, U., Strobl, L. J., Honjo, T., Clevers, H., & Radtke, F. (2008). Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27Kip1 and p57Kip2. EMBO Reports, 9(4), 377-383. https://doi.org/10.1038/embor.2008.7

@article{fa8f9f0693fb43cf9c087d3beacc89ac,

title = "Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27Kip1 and p57Kip2.",

abstract = "The crucial role of individual Notch receptors and the mechanism by which they maintain intestinal crypt progenitor cells were assessed by using a series of inducible gut-specific Notch mutant mice. We found that Notch1 and Notch2 receptors function redundantly in the gut, as only simultaneous loss of both receptors results in complete conversion of proliferating crypt progenitors into post-mitotic goblet cells. This conversion correlates with the loss of Hes1 expression and derepression of the cyclin-dependent kinase (CDK) inhibitors p27Kip1 and p57Kip2. We also found that the promoter of both CDK inhibitor genes is occupied by the Notch effector Hes1 in wild-type crypt progenitor cells. Thus, our results indicate that Notch-mediated Hes1 expression contributes to the maintenance of the proliferative crypt compartment of the small intestine by transcriptionally repressing two CDK inhibitors.",

author = "O. Riccio and {van Gijn}, M.E. and A.C. Bezdek and L. Pellegrinet and {van Es}, J.H. and U. Zimber-Strobl and L.J. Strobl and T. Honjo and H. Clevers and F. Radtke",

note = "Reporting year: 2008",

year = "2008",

doi = "10.1038/embor.2008.7",

language = "English",

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pages = "377--383",

journal = "EMBO Reports",

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Riccio, O, van Gijn, ME, Bezdek, AC, Pellegrinet, L, van Es, JH, Zimber-Strobl, U, Strobl, LJ, Honjo, T, Clevers, H & Radtke, F 2008, 'Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27Kip1 and p57Kip2.', EMBO Reports, vol. 9, nr. 4, blz. 377-383. https://doi.org/10.1038/embor.2008.7

Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27Kip1 and p57Kip2. / Riccio, O.; van Gijn, M.E.; Bezdek, A.C. et al.
In: EMBO Reports, Vol. 9, Nr. 4, 2008, blz. 377-383.

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

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AU - Riccio, O.

AU - van Gijn, M.E.

AU - Bezdek, A.C.

AU - Pellegrinet, L.

AU - van Es, J.H.

AU - Zimber-Strobl, U.

AU - Strobl, L.J.

AU - Honjo, T.

AU - Clevers, H.

AU - Radtke, F.

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AB - The crucial role of individual Notch receptors and the mechanism by which they maintain intestinal crypt progenitor cells were assessed by using a series of inducible gut-specific Notch mutant mice. We found that Notch1 and Notch2 receptors function redundantly in the gut, as only simultaneous loss of both receptors results in complete conversion of proliferating crypt progenitors into post-mitotic goblet cells. This conversion correlates with the loss of Hes1 expression and derepression of the cyclin-dependent kinase (CDK) inhibitors p27Kip1 and p57Kip2. We also found that the promoter of both CDK inhibitor genes is occupied by the Notch effector Hes1 in wild-type crypt progenitor cells. Thus, our results indicate that Notch-mediated Hes1 expression contributes to the maintenance of the proliferative crypt compartment of the small intestine by transcriptionally repressing two CDK inhibitors.

U2 - 10.1038/embor.2008.7

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Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27Kip1 and p57Kip2.

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