title: Targeted disruption of Sonic Hedgehog in the mouse adrenal leads to adrenocortical hypoplasia.
abstract: Development of the mammalian adrenal gland is regulated by a diverse network of growth and transcription factors. Disruptions in these pathways often result in adrenal insufficiency because of adrenal hypoplasia. Several lines of evidence have suggested that the Hedgehog signaling pathway, which controls many aspects of tissue and organ patterning, may play a direct role in adrenal morphogenesis as well. Therefore, we examined the role of Sonic Hedgehog (Shh), a member of the Hedgehog family, in mouse adrenal development. We show that Shh and its downstream effectors Gli1, Gli2, and Gli3 are expressed in the adrenal cortex throughout development, and that Shh is required for normal adrenal organogenesis. Conditional inactivation of Shh in the adrenal cortex using a Cre-loxP system resulted in severe hypoplasia and disorganization of the cortex. In mice carrying the targeted mutation (Shh(fl/fl;SF-1/Cre+)), adrenal mass was significantly reduced and the cortex failed to encapsulate the adrenal medulla. Taken together, these results establish a direct role for Shh signaling in normal adrenal development.
authors.affiliation: Department of Human Genetics, University of California, Los Angeles, California, USA.
authors.forename: Saunders
authors.initials: S
authors.lastname: Ching
authors.forename: Eric
authors.initials: E
authors.lastname: Vilain
mesh_terms: D000302:Adrenal Cortex / Q000254:growth & development* / Q000378:metabolism; D000818:Animals; D017931:DNA Primers / Q000235:genetics; D020868:Gene Silencing; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism; D038081:Organogenesis / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
chemical_list: D017931:DNA Primers; C000618551:Gli2 protein, mouse; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D015534:Trans-Activators; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3