Dasen, JS;
Martinez Barbera, JP;
Herman, TS;
Connell, SO;
Olson, L;
Ju, B;
Tollkuhn, J;
... Rosenfeld, MG; + view all
(2001)
Temporal regulation of a paired-like homeodomain repressor/TLE corepressor complex and a related activator is required for pituitary organogenesis.
Genes and Development
, 15
(23)
pp. 3193-3207.
10.1101/gad.932601.
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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.
| Type: | Article |
|---|---|
| Title: | Temporal regulation of a paired-like homeodomain repressor/TLE corepressor complex and a related activator is required for pituitary organogenesis. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1101/gad.932601 |
| Publisher version: | http://dx.doi.org/10.1101/gad.932601 |
| Language: | English |
| Additional information: | Originally published by Cold Spring Harbor Laboratory Press. Distributed under the Creative Commons Attribution-Non-Commercial 4.0 International License (CC-BY-NC), as described at http://creativecommons.org/licenses/by-nc/4.0/. This license permits non-commercial use, including reproduction, adaptation, and distribution of the article provided the original author and source are credited. |
| Keywords: | Animals, Basic Helix-Loop-Helix Transcription Factors, Blotting, Western, Cell Lineage, Co-Repressor Proteins, Embryonic and Fetal Development, Evolution, Molecular, Feedback, Physiological, Fibroblast Growth Factors, Gene Expression Regulation, Developmental, HeLa Cells, Homeodomain Proteins, Humans, In Situ Hybridization, Macromolecular Substances, Mice, Mice, Transgenic, Models, Biological, Mutation, Nuclear Proteins, Pituitary Gland, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Repressor Proteins, Trans-Activators |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/8127 |
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