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PMID:9806931

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Citation

Takuma, N, Sheng, HZ, Furuta, Y, Ward, JM, Sharma, K, Hogan, BL, Pfaff, SL, Westphal, H, Kimura, S and Mahon, KA (1998) Formation of Rathke's pouch requires dual induction from the diencephalon. Development 125:4835-40

Abstract

Targeted disruption of the homeobox gene T/ebp (Nkx2.1, Ttf1, Titf1) in mice results in ablation of the pituitary. Paradoxically, while T/ebp is expressed in the ventral diencephalon during forebrain formation, it is not expressed in Rathke's pouch or in the pituitary gland at any time of embryogenesis. Examination of pituitary development in the T/ebp homozygous null mutant embryos revealed that a pouch rudiment is initially formed but is eliminated by programmed cell death before formation of a definitive pouch. In the diencephalon of the mutant, Bmp4 expression is maintained, whereas Fgf8 expression is not detectable. These data and additional genetic and molecular observations suggest that Rathke's pouch develops in a two-step process that requires at least two sequential inductive signals from the diencephalon. First, BMP4 is required for induction and formation of the pouch rudiment, a role confirmed by analysis of Bmp4 homozygous null mutant embryos. Second, FGF8 is necessary for activation of the key regulatory gene Lhx3 and subsequent development of the pouch rudiment into a definitive pouch. This study provides firm molecular genetic evidence that morphogenesis of the pituitary primordium is induced in vivo by signals from the adjacent diencephalon.

Links

PubMed

Keywords

Animals; Apoptosis; Diencephalon/embryology; Embryonic Induction; Embryonic and Fetal Development; Gestational Age; Homeodomain Proteins/physiology; Homozygote; In Situ Hybridization; Mice; Mice, Knockout; Nuclear Proteins/deficiency; Nuclear Proteins/genetics; Nuclear Proteins/physiology; Pituitary Gland, Anterior/abnormalities; Pituitary Gland, Anterior/embryology; Transcription Factors/deficiency; Transcription Factors/genetics; Transcription Factors/physiology

Significance

Annotations

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

MOUSE:BMP4

acts_upstream_of_or_within

GO:0021983: pituitary gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857137

P

  • results_in_development_of:(EMAPA:16574)

Seeded From UniProt

complete

MOUSE:BMP4

acts_upstream_of_or_within

GO:0001759: organ induction

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857137

P

Seeded From UniProt

complete

MOUSE:NKX21

acts_upstream_of_or_within

GO:0021983: pituitary gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857494

P

  • results_in_development_of:(EMAPA:16899)|results_in_development_of:(EMAPA:16725)

Seeded From UniProt

complete

MOUSE:NKX21

acts_upstream_of_or_within

GO:0031128: developmental induction

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857494

P

Seeded From UniProt

complete

MOUSE:ISL1

acts_upstream_of_or_within

GO:0021983: pituitary gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2182246

P

  • results_in_development_of:(EMAPA:16725)

Seeded From UniProt

complete

MOUSE:BMP4

acts_upstream_of_or_within

GO:0001759: organ induction

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857137

P

regulates_o_results_in_development_of:(EMAPA:16512)|regulates_o_results_in_development_of:(EMAPA:16574)

Seeded From UniProt

complete

MOUSE:BMP4

acts_upstream_of_or_within

GO:0021983: pituitary gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857137

P

results_in_development_of:(EMAPA:16574)

Seeded From UniProt

complete

MOUSE:NKX21

acts_upstream_of_or_within

GO:0031128: developmental induction

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857494

P

has_participant:(EMAPA:16899)|has_participant:(EMAPA:16725)

Seeded From UniProt

complete

MOUSE:NKX21

acts_upstream_of_or_within

GO:0021983: pituitary gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857494

P

results_in_development_of:(EMAPA:16899)|results_in_development_of:(EMAPA:16725)

Seeded From UniProt

complete

MOUSE:ISL1

acts_upstream_of_or_within

GO:0021983: pituitary gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2182246

P

results_in_development_of:(EMAPA:16725)

Seeded From UniProt

complete


See also

References

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