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Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development

Gaston-Massuet, C; Andoniadou, CL; Signore, M; Sajedi, E; Bird, S; Turner, JMA; Martinez-Barbera, JP; (2008) Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development. DEV BIOL , 324 (2) 322 - 333. 10.1016/j.ydbio.2008.08.008.

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Abstract

Hesx1 has been shown to be essential for normal pituitary development. The homeobox gene Six3 is expressed in the developing pituitary gland during mouse development but its function in this tissue has been precluded by the fact that in the Six3-deficient embryos the pituitary gland is not induced. To gain insights into the function of Six3 during pituitary development we have generated Six3(+/-);Hesx1(Cre/+) double heterozygous mice. Strikingly, these mice show marked dwarfism, which is first detectable around weaning, and die by the 5th-6th week of age. Thyroid and gonad development is also impaired in these animals. Analysis of Six3(+/-);Hesx1(Cre/+) compound embryos indicates that hypopituitarism is the likely cause of these defects since pituitary development is severely impaired in these mutants. Similar to the Hesx1-deficient embryos, Rathke's pouch is initially expanded in Six3(+/-);Hesx1(Cre/+) compound embryos due to an increase in cell proliferation. Subsequently, the anterior pituitary gland appears bifurcated, dysmorphic and occasionally ectopically misplaced in the nasopharyngeal cavity, but cell differentiation is unaffected. Our research has revealed a role for Six3 in normal pituitary development, which has likely been conserved during evolution as SIX3 is also expressed in the pituitary gland of the human embryo. (C) 2008 Elsevier Inc. All rights reserved.

Type: Article
Title: Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development
DOI: 10.1016/j.ydbio.2008.08.008
Keywords: HESX1, SIX3, Ectopic pituitary, Wnt/beta-catenin, ANTERIOR NEURAL PLATE, GROWTH-HORMONE, LINEAGE DETERMINATION, EYE DEVELOPMENT, MOLECULAR-BASIS, BETA-CATENIN, MOUSE EMBRYO, PROLIFERATION, HOMEODOMAIN, MUTATIONS
UCL classification: 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 Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Development Bio and Cancer Prog
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Developmental Neurosciences Prog
UCL > Provost and Vice Provost Offices > VP Health
UCL > Provost and Vice Provost Offices > VP Health > Translational Research Office
URI: http://discovery.ucl.ac.uk/id/eprint/69105
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