Zhu, X., Zhang, J., Tollkuhn, J., Ohsawa, R., Bresnick, E. H., Guillemot, F., Kageyama, R., Rosenfeld, M. G. (October 2006) Sustained Notch signaling in progenitors is required for sequential emergence of distinct cell lineages during organogenesis. Genes Dev, 20 (19). pp. 2739-53. ISSN 0890-9369 (Print)0890-9369 (Linking)
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Abstract
Mammalian organogenesis results from the concerted actions of signaling pathways in progenitor cells that induce a hierarchy of regulated transcription factors critical for organ and cell type determination. Here we demonstrate that sustained Notch activity is required for the temporal maintenance of specific cohorts of proliferating progenitors, which underlies the ability to specify late-arising cell lineages during pituitary organogenesis. Conditional deletion of Rbp-J, which encodes the major mediator of the Notch pathway, leads to premature differentiation of progenitor cells, a phenotype recapitulated by loss of the basic helix-loop-helix (bHLH) factor Hes1, as well as a conversion of the late (Pit1) lineage into the early (corticotrope) lineage. Notch signaling is required for maintaining expression of the tissue-specific paired-like homeodomain transcription factor, Prop1, which is required for generation of the Pit1 lineage. Attenuation of Notch signaling is necessary for terminal differentiation in post-mitotic Pit1+ cells, and the Notch-repressed Pit1 target gene, Math3, is specifically required for maturation and proliferation of the GH-producing somatotrope. Thus, sustained Notch signaling in progenitor cells is required to prevent conversion of the late-arising cell lineages to early-born cell lineages, permitting specification of diverse cell types, a strategy likely to be widely used in mammalian organogenesis.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Animals Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism/physiology Cell Differentiation/genetics/physiology Cell Lineage/genetics/ physiology Female Gene Expression Regulation, Developmental/genetics Homeodomain Proteins/genetics/metabolism In Situ Hybridization, Fluorescence/methods Male Mice Mice, Knockout Mice, Transgenic Models, Biological Nerve Tissue Proteins/genetics/metabolism Organogenesis/genetics/ physiology Pituitary Gland/embryology/metabolism Polymerase Chain Reaction/methods Receptors, Notch/genetics/metabolism/ physiology Signal Transduction/genetics/ physiology Stem Cells/cytology/metabolism/ physiology Transcription Factor Pit-1/genetics/metabolism |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > Notch organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > organs types and functions > organogenesis organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell |
| CSHL Authors: | |
| Communities: | CSHL labs > Tollkuhn lab |
| Depositing User: | Matt Covey |
| Date: | 1 October 2006 |
| Date Deposited: | 23 Jul 2015 20:06 |
| Last Modified: | 23 Jul 2015 20:06 |
| PMCID: | PMC1578699 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/31658 |
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