Document Detail


Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development.
MedLine Citation:
PMID:  18775421     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Carles Gaston-Massuet; Cynthia L Andoniadou; Massimo Signore; Ezat Sajedi; Sophie Bird; James M A Turner; Juan Pedro Martinez-Barbera
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-08-18
Journal Detail:
Title:  Developmental biology     Volume:  324     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-01     Completed Date:  2008-12-04     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  322-33     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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:
068630//Wellcome Trust; 068630//Wellcome Trust; 078432//Wellcome Trust; 078432//Wellcome Trust; MC_U117588498//Medical Research Council
Chemical
Reg. No./Substance:
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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