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PMID:12221011

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Citation

Lamm, ML, Catbagan, WS, Laciak, RJ, Barnett, DH, Hebner, CM, Gaffield, W, Walterhouse, D, Iannaccone, P and Bushman, W (2002) Sonic hedgehog activates mesenchymal Gli1 expression during prostate ductal bud formation. Dev. Biol. 249:349-66

Abstract

Ductal budding in the developing prostate is a testosterone-dependent event that involves signaling between the urogenital sinus epithelium (UGE) and urogenital sinus mesenchyme (UGM). We show here that ductal bud formation is associated with focused expression of Sonic hedgehog (Shh) in the epithelium of nascent prostate buds and in the growing tips of elongating prostate ducts. This pattern of localized Shh expression occurs in response to testosterone stimulation. The gene for the Shh receptor, Ptc1, is expressed in the UGM, as are the members of the Gli gene family of transcriptional regulators (Gli1, Gli2, and Gli3). Expression of Ptc1, Gli1, and Gli2 is localized primarily to mesenchyme surrounding prostate buds, whereas Gli3 is expressed diffusely throughout the UGM. A strong dependence of Gli1 (and Ptc1) expression on Shh signaling is demonstrated by induction of expression in both the intact urogenital sinus and the isolated UGM by exogenous SHH peptide. A similar dependence of Gli2 and Gli3 expression on Shh is not observed. Nonetheless, the chemical inhibitor of Shh signaling, cyclopamine, produced a graded inhibition of Gli gene expression (Gli1>Gli2>Gli3) in urogenital sinus explants that was paralleled by a severe inhibition of ductal budding.

Links

PubMed

Keywords

Animals; Base Sequence; Cell Division; DNA Primers; Dihydrotestosterone/pharmacology; Diosgenin; Embryonic and Fetal Development/physiology; Epithelial Cells/cytology; Epithelium/embryology; Gene Expression Regulation, Developmental/drug effects; Hedgehog Proteins; In Situ Hybridization; Male; Mesoderm/physiology; Mice; Oncogene Proteins/genetics; Organ Culture Techniques/methods; Prostate/cytology; Prostate/embryology; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction/physiology; Solanaceous Alkaloids/pharmacology; Trans-Activators/drug effects; Trans-Activators/genetics; Trans-Activators/physiology; Transcription Factors/genetics; Veratrum Alkaloids/pharmacology; Zinc Fingers

Significance

Annotations

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

HUMAN:SHH

acts_upstream_of_or_within

GO:0060738: epithelial-mesenchymal signaling involved in prostate gland development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0060783: mesenchymal smoothened signaling pathway involved in prostate gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000134)
  • occurs_in:(EMAPA:18995)

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0060685: regulation of prostatic bud formation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • regulates_o_occurs_in:(CL:0000066)
  • regulates_o_results_in_formation_of:(EMAPA:18995)

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0060685: regulation of prostatic bud formation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • regulates_o_results_in_formation_of:(EMAPA:18995)
  • regulates_o_has_participant:(CL:0000066)

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0060738: epithelial-mesenchymal signaling involved in prostate gland development

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:Q15465

P

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0060768: regulation of epithelial cell proliferation involved in prostate gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0060769: positive regulation of epithelial cell proliferation involved in prostate gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0060782: regulation of mesenchymal cell proliferation involved in prostate gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0060783: mesenchymal smoothened signaling pathway involved in prostate gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(EMAPA:18995)
  • occurs_in:(CL:0000134)

Seeded From UniProt

complete

HUMAN:SHH

involved_in

GO:0060738: epithelial-mesenchymal signaling involved in prostate gland development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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