Constitutive Musashi1 expression impairs mouse postnatal development and intestinal homeostasis
View/ Open
Issue Date
2020-12-29Author
Chiremba, Thelma T.
Neufeld, Kristi L.
Publisher
American Society for Cell Biology
Type
Article
Article Version
Scholarly/refereed, publisher version
Rights
© 2021 Chiremba and Neufeld. This article is distributed by The American Society for Cell Biology under license from the author(s). This work is licensed under a Creative Commons Attribution-NonCommercial ShareAlike 3.0 International License.
Metadata
Show full item recordAbstract
Evolutionarily conserved RNA-binding protein Musashi1 (Msi1) can regulate developmentally relevant genes. Here we report the generation and characterization of a mouse model that allows inducible Msi1 overexpression in a temporal and tissue-specific manner. We show that ubiquitous Msi1 induction in ∼5-wk-old mice delays overall growth, alters organ-to-body proportions, and causes premature death. Msi1-overexpressing mice had shortened intestines, diminished intestinal epithelial cell (IEC) proliferation, and decreased growth of small intestine villi and colon crypts. Although Lgr5-positive intestinal stem cell numbers remained constant in Msi1-overexpressing tissue, an observed reduction in Cdc20 expression provided a potential mechanism underlying the intestinal growth defects. We further demonstrated that Msi1 overexpression affects IEC differentiation in a region-specific manner, with ileum tissue being influenced the most. Ilea of mutant mice displayed increased expression of enterocyte markers, but reduced expression of the goblet cell marker Mucin2 and fewer Paneth cells. A higher hairy and enhancer of split 1:mouse atonal homolog 1 ratio in ilea from Msi1-overexpressing mice implicated Notch signaling in inducing enterocyte differentiation. Together, this work implicates Msi1 in mouse postnatal development of multiple organs, with Notch signaling alterations contributing to intestinal defects. This new mouse model will be a useful tool to further elucidate the role of Msi1 in other tissue settings.
Collections
Citation
Chiremba, T. T., & Neufeld, K. L. (2021). Constitutive Musashi1 expression impairs mouse postnatal development and intestinal homeostasis. Molecular biology of the cell, 32(1), 28–44. https://doi.org/10.1091/mbc.E20-03-0206
Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.
Except where otherwise noted, this item's license is described as: © 2021 Chiremba and Neufeld. This article is distributed by The American Society for Cell Biology under license from the author(s). This work is licensed under a Creative Commons Attribution-NonCommercial ShareAlike 3.0 International License.