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PMID:17919533

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Citation

Brinkmeier, ML, Potok, MA, Davis, SW and Camper, SA (2007) TCF4 deficiency expands ventral diencephalon signaling and increases induction of pituitary progenitors. Dev. Biol. 311:396-407

Abstract

The anterior and intermediate lobes of the pituitary gland are formed from Rathke's pouch. FGF, BMP and WNT signals emanating from the ventral diencephalon influence pouch growth and development. In order to examine the role of canonical WNT signaling during pituitary development we examined the pituitary expression of the TCF/LEF family of transcription factors, which mediate WNT signaling through the binding of beta-catenin. We report here the expression of several members of this family during pituitary development and the functional role of one member, TCF4 (TCF7L2), in the induction of the pituitary primordium. TCF4 is expressed in the ventral diencephalon early in pituitary development, rostral to a domain of BMP and FGF expression. Tcf4 deficient mice express Fgf10 and Bmp4; however, the Bmp and Fgf expression domains are expanded rostrally. As a result, additional pituitary progenitor cells are recruited into Rathke's pouch in Tcf4 mutants. Mutants also exhibit an expansion of the Six6 expression domain within Rathke's pouch, which may increase the number of proliferating pouch cells, resulting in a greatly enlarged anterior pituitary gland. This suggests that TCF4 negatively regulates pituitary growth through two mechanisms. The first mechanism is to restrict the domains of BMP and FGF signaling in the ventral diencephalon, and the second mechanism is the restriction of Six6 within Rathke's pouch. Thus, TCF4 is necessary both intrinsically and extrinsically to Rathke's pouch to ensure the proper growth of the pituitary gland.

Links

PubMed PMC2693283 Online version:10.1016/j.ydbio.2007.08.046

Keywords

Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Bone Morphogenetic Proteins/genetics; Bone Morphogenetic Proteins/metabolism; Cell Death; Cell Proliferation; Diencephalon/anatomy & histology; Diencephalon/physiology; Female; Fibroblast Growth Factors/genetics; Fibroblast Growth Factors/metabolism; In Situ Hybridization; Lymphoid Enhancer-Binding Factor 1/genetics; Lymphoid Enhancer-Binding Factor 1/metabolism; Mice; Mice, Knockout; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Pituitary Gland/abnormalities; Pituitary Gland/anatomy & histology; Pituitary Gland/embryology; Pituitary Gland/metabolism; Protein Isoforms/genetics; Protein Isoforms/metabolism; Signal Transduction/physiology; Stem Cells/cytology; Stem Cells/physiology; TCF Transcription Factors/genetics; TCF Transcription Factors/metabolism; Transcription Factor 7-Like 1 Protein

Significance

Annotations

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

MOUSE:TF7L2

acts_upstream_of_or_within

GO:0030514: negative regulation of BMP signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1926344

P

  • regulates_o_occurs_in:(EMAPA:16725)

Seeded From UniProt

complete

MOUSE:TF7L2

acts_upstream_of_or_within

GO:0021983: pituitary gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1926344

P

  • results_in_development_of:(EMAPA:16725)

Seeded From UniProt

complete

MOUSE:TF7L2

acts_upstream_of_or_within

GO:0046621: negative regulation of organ growth

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1926344

P

  • regulates_o_occurs_in:(EMAPA:16898)

Seeded From UniProt

complete

MOUSE:TF7L2

acts_upstream_of_or_within

GO:0043065: positive regulation of apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1926344

P

  • occurs_in:(EMAPA:16725)

Seeded From UniProt

complete

MOUSE:TF7L2

acts_upstream_of_or_within

GO:0040037: negative regulation of fibroblast growth factor receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1926344

P

  • regulates_o_occurs_in:(EMAPA:16725)

Seeded From UniProt

complete


See also

References

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