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PMID:18775421

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Citation

Gaston-Massuet, C, Andoniadou, CL, Signore, M, Sajedi, E, Bird, S, Turner, JM and Martinez-Barbera, JP (2008) Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development. Dev. Biol. 324:322-33

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+/- ;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.

Links

PubMed PMC3606136 Online version:10.1016/j.ydbio.2008.08.008

Keywords

Animals; Cell Differentiation; Cell Proliferation; Dwarfism, Pituitary/genetics; Eye Proteins/genetics; Eye Proteins/metabolism; Gene Expression Regulation, Developmental; Genes, Homeobox; Genotype; Gonads/abnormalities; Gonads/cytology; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Humans; Mice; Mice, Inbred C57BL; Mutation; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Pituitary Gland, Anterior/cytology; Pituitary Gland, Anterior/embryology; Pituitary Gland, Anterior/metabolism; Repressor Proteins; Thyroid Gland/abnormalities; Thyroid Gland/cytology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:HESX1

acts_upstream_of_or_within

GO:0021983: pituitary gland development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:102764

P

  • has_input:(MGI:MGI:102764)

Seeded From UniProt

complete

MOUSE:HESX1

acts_upstream_of_or_within

GO:0008406: gonad development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:102764

P

  • has_input:(MGI:MGI:102764)

Seeded From UniProt

complete

MOUSE:HESX1

acts_upstream_of_or_within

GO:0030878: thyroid gland development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:102764

P

  • has_input:(MGI:MGI:102764)

Seeded From UniProt

complete

MOUSE:HESX1

acts_upstream_of_or_within

GO:0035264: multicellular organism growth

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:102764

P

  • has_input:(MGI:MGI:102764)

Seeded From UniProt

complete

MOUSE:SIX3

acts_upstream_of_or_within

GO:0021983: pituitary gland development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:96071

P

  • has_input:(MGI:MGI:96071)

Seeded From UniProt

complete

MOUSE:SIX3

acts_upstream_of_or_within

GO:0008406: gonad development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:96071

P

  • has_input:(MGI:MGI:96071)

Seeded From UniProt

complete

MOUSE:SIX3

acts_upstream_of_or_within

GO:0030878: thyroid gland development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:96071

P

  • has_input:(MGI:MGI:96071)

Seeded From UniProt

complete

MOUSE:SIX3

acts_upstream_of_or_within

GO:0035264: multicellular organism growth

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:96071

P

  • has_input:(MGI:MGI:96071)

Seeded From UniProt

complete

MOUSE:SIX3

involved_in

GO:0042127: regulation of cell population proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SIX3

involved_in

GO:0021983: pituitary gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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