UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Temporal regulation of a paired-like homeodomain repressor/TLE corepressor complex and a related activator is required for pituitary organogenesis.

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. Green open access

[img]
Preview
Text
Dasen et al_8127_Temporal regulation of a paired-like homeodomain repressor_2001.pdf - Published version

Download (1MB) | Preview

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
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
Downloads since deposit
37Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item