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PMID:18996108

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Citation

Himes, AD and Raetzman, LT (2009) Premature differentiation and aberrant movement of pituitary cells lacking both Hes1 and Prop1. Dev. Biol. 325:151-61

Abstract

In the pituitary, the transition from proliferating progenitor cell into differentiated hormone producing cell is carefully regulated in a time-dependent and spatially-restricted manner. We report that two targets of Notch signaling, Hes1 and Prop1, are needed to maintain progenitors within Rathke's pouch and for the restriction of differentiated cells to the ventral pituitary. We observed ACTH and alphaGSU producing cells that had prematurely differentiated within Rathke's pouch along with correlated ectopic expression of Mash1 only when both Prop1 and Hes1 were lost. We also discovered that downregulation of N-cadherin expression in cells as they transition from Rathke's pouch to the anterior lobe appears to be essential for their movement. In the Prop1 mutant, cells are trapped in Rathke's pouch and N-cadherin expression remains high. Also, Slug, a marker of epithelial-to-mesenchymal transition, is absent in the dorsal anterior lobe. When Hes1 is lost in the Prop1 mutant, N-cadherin is downregulated and cells are able to exit Rathke's pouch but have lost their migrational cues and form ectopic foci surrounding Rathke's pouch. Our data reveal important overlapping functions of Hes1 and Prop1 in cell differentiation and movement that are critical for pituitary organogenesis.

Links

PubMed PMC2642967 Online version:10.1016/j.ydbio.2008.10.010

Keywords

Animals; Basic Helix-Loop-Helix Transcription Factors/deficiency; Basic Helix-Loop-Helix Transcription Factors/genetics; Basic Helix-Loop-Helix Transcription Factors/metabolism; Body Patterning; Cadherins/genetics; Cadherins/metabolism; Cell Differentiation; Cell Lineage; Cell Movement; Corticotrophs/cytology; Corticotrophs/metabolism; Gene Expression Regulation, Developmental; Gonadotrophs/cytology; Gonadotrophs/metabolism; Homeodomain Proteins/metabolism; Mice; Mice, Inbred C57BL; Models, Biological; Mutation/genetics; Organogenesis; Pituitary Gland/cytology; Pituitary Gland/embryology; Pituitary Gland/metabolism; Transcription Factor Pit-1/metabolism; Transcription Factors/metabolism

Significance

Annotations

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

MOUSE:HES1

acts_upstream_of_or_within

GO:0021984: adenohypophysis development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3808031

P

  • results_in_development_of:(EMAPA:17518)

Seeded From UniProt

complete

MOUSE:HES1

acts_upstream_of_or_within

GO:0016477: cell migration

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:109330

P

  • occurs_in:(EMAPA:16898)

Seeded From UniProt

complete

MOUSE:PROP1

acts_upstream_of_or_within

GO:0021984: adenohypophysis development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • results_in_development_of:(EMAPA:17515)

Seeded From UniProt

complete

MOUSE:PROP1

acts_upstream_of_or_within

GO:0016477: cell migration

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:104853

P

  • occurs_in:(EMAPA:16898)

Seeded From UniProt

complete


See also

References

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