| Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development. | |
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MedLine Citation:
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PMID: 18775421 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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+/- ;Hesx1Cre/+ 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+/- ;Hesx1Cre/+ 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+/- ;Hesx1Cre/+ 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. |
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Authors:
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Carles Gaston-Massuet; Cynthia L Andoniadou; Massimo Signore; Ezat Sajedi; Sophie Bird; James M A Turner; Juan Pedro Martinez-Barbera |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-08-18 |
Journal Detail:
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Title: Developmental biology Volume: 324 ISSN: 1095-564X ISO Abbreviation: Dev. Biol. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-12-01 Completed Date: 2008-12-04 Revised Date: 2013-04-18 |
Medline Journal Info:
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Nlm Unique ID: 0372762 Medline TA: Dev Biol Country: United States |
Other Details:
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Languages: eng Pagination: 322-33 Citation Subset: IM |
Affiliation:
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Neural Development Unit, Institute of Child Health, University College London, London, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Differentiation Cell Proliferation Dwarfism, Pituitary / genetics Eye Proteins / genetics, metabolism* Gene Expression Regulation, Developmental* Genes, Homeobox Genotype Gonads / abnormalities, cytology Homeodomain Proteins / genetics, metabolism* Humans Mice Mice, Inbred C57BL Mutation Nerve Tissue Proteins / genetics, metabolism* Pituitary Gland, Anterior / cytology, embryology*, metabolism Repressor Proteins Thyroid Gland / abnormalities, cytology |
| Grant Support | |
ID/Acronym/Agency:
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068630//Wellcome Trust; 068630//Wellcome Trust; 078432//Wellcome Trust; 078432//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/Eye Proteins; 0/Hesx1 protein, mouse; 0/Homeodomain Proteins; 0/Nerve Tissue Proteins; 0/Repressor Proteins; 0/Sine oculis homeobox homolog 3 protein |
| Comments/Corrections | |
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