Dasen, J. S., Martinez Barbera, J. P., Herman, T. S., Connell, S. O., Olson, L., Ju, B., Tollkuhn, J., Baek, S. H., Rose, D. W., Rosenfeld, M. G. (December 2001) Temporal regulation of a paired-like homeodomain repressor/TLE corepressor complex and a related activator is required for pituitary organogenesis. Genes Dev, 15 (23). pp. 3193-207. ISSN 0890-9369 (Print)0890-9369 (Linking)
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Abstract
Understanding the functional significance of the coordinate expression of specific corepressors and DNA-binding transcription factors remains a critical question in mammalian development. During the development of the pituitary gland, two highly related paired-like homeodomain factors, a repressor, Hesx1/Rpx and an activator, Prop-1, are expressed in sequential, overlapping temporal patterns. Here we show that while the repressive actions of Hesx1/Rpx may be required for initial pituitary organ commitment, progression beyond the appearance of the first pituitary (POMC) lineage requires both loss of Hesx1 expression and the actions of Prop-1. Although Hesx1 recruits both the Groucho-related corepressor TLE1 and the N-CoR/Sin3/HDAC complex on distinct domains, the repressor functions of Hesx1 in vivo prove to require the specific recruitment of TLE1, which exhibits a spatial and temporal pattern of coexpression during pituitary organogenesis. Furthermore, Hesx1-mediated repression coordinates a negative feedback loop with FGF8/FGF10 signaling in the ventral diencephalon, required to prevent induction of multiple pituitary glands from oral ectoderm. Our data suggest that the opposing actions of two structurally-related DNA-binding paired-like homeodomain transcription factors, binding to similar cognate elements, coordinate pituitary organogenesis by reciprocally repressing and activating target genes in a temporally specific fashion, on the basis of the actions of a critical, coexpressed TLE corepressor.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Animals Basic Helix-Loop-Helix Transcription Factors Blotting, Western Cell Lineage Co-Repressor Proteins Embryonic and Fetal Development/ genetics Evolution, Molecular Feedback, Physiological Fibroblast Growth Factors/metabolism Gene Expression Regulation, Developmental HeLa Cells Homeodomain Proteins/chemistry/genetics/ metabolism Humans In Situ Hybridization Macromolecular Substances Mice Mice, Transgenic Models, Biological Mutation/genetics Nuclear Proteins/genetics/metabolism Pituitary Gland/cytology/ embryology/metabolism Precipitin Tests Protein Binding Protein Structure, Tertiary Repressor Proteins/chemistry/genetics/ metabolism Trans-Activators/chemistry/genetics/ metabolism |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > homeodomain protein organs, tissues, organelles, cell types and functions > tissues types and functions > pituitary gland |
| CSHL Authors: | |
| Communities: | CSHL labs > Tollkuhn lab |
| Depositing User: | Matt Covey |
| Date: | 1 December 2001 |
| Date Deposited: | 23 Jul 2015 19:10 |
| Last Modified: | 23 Jul 2015 19:10 |
| PMCID: | PMC312840 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/31662 |
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