UMMS Affiliation
Program in Molecular Medicine
Publication Date
2015-12-01
Document Type
Article
Disciplines
Cell Biology
Abstract
The Drosophila adult midgut contains intestinal stem cells that support homeostasis and repair. We show here that the leucine zipper protein Bunched and the adaptor protein Madm are novel regulators of intestinal stem cells. MARCM mutant clonal analysis and cell type specific RNAi revealed that Bunched and Madm were required within intestinal stem cells for proliferation. Transgenic expression of a tagged Bunched showed a cytoplasmic localization in midgut precursors, and the addition of a nuclear localization signal to Bunched reduced its function to cooperate with Madm to increase intestinal stem cell proliferation. Furthermore, the elevated cell growth and 4EBP phosphorylation phenotypes induced by loss of Tuberous Sclerosis Complex or overexpression of Rheb were suppressed by the loss of Bunched or Madm. Therefore, while the mammalian homolog of Bunched, TSC-22, is able to regulate transcription and suppress cancer cell proliferation, our data suggest the model that Bunched and Madm functionally interact with the TOR pathway in the cytoplasm to regulate the growth and subsequent division of intestinal stem cells.
Keywords
UMCCTS funding, Bunched, Drosophila, Intestine, Madm, Stem cells, TSC-22, Tuberous sclerosis complex
Rights and Permissions
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/ licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
DOI of Published Version
10.1007/s12015-015-9617-5
Source
Stem Cell Rev. 2015 Dec;11(6):813-25. doi: 10.1007/s12015-015-9617-5. Link to article on publisher's site
Journal/Book/Conference Title
Stem cell reviews
Related Resources
PubMed ID
26323255
Repository Citation
Nie Y, Li Q, Amcheslavsky A, Duhart JC, Veraksa A, Stocker H, Raftery LA, Ip YT. (2015). Bunched and Madm Function Downstream of Tuberous Sclerosis Complex to Regulate the Growth of Intestinal Stem Cells in Drosophila. Open Access Articles. https://doi.org/10.1007/s12015-015-9617-5. Retrieved from https://escholarship.umassmed.edu/oapubs/2656
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.