SFEBES2011 Symposia The novel role of primary cilia in endocrine disease and obesity (4 abstracts)
Sonic hedgehog signalling and primary cilia in the adrenal
Katy Cogger 1 , Leo Guasti 1 , Zahida Banu 1 , Phil Beales 3 , Alex Paul 2 , Ed Laufer 2 & Peter King 1
1WHRI, Queen Mary University of London, London, UK; 2Columbia University, New York, New York, USA; 3Institute of Child Health, London, UK.
The adrenogonadal primordium develops from a thickening of the coelomic epithelium covering the urogenital ridge. After segregation of the primordium into the bipotential gonad and the adrenocortical primordium, the cortex is encapsulated by mesenchymal cells and infiltrated by migrating sympathoadrenal cells, which form the medulla. We have shown that the cell fate regulator sonic hedgehog (Shh) is not required for the formation of the adrenocortical primordium but is required for its subsequent growth and development. Its expression is restricted to relatively undifferentiated cortical subcapsular cells and it signals to cells within the capsule. Lineage tracing studies in mice demonstrate that these signal receiving cells enter the cortex and adopt a steroidogenic phenotype, becoming zona glomerulosa and zona fasciculata cells, at least in part, via a Shh-expressing intermediate cell population.
The primary cilium is required for hedgehog (Hh) signalling, with disruption of genes required for cilia formation phenocopying Hh pathway mutations. Although there has been no report of ciliopathies associated with adrenal insufficiency to date, our studies have documented adrenal phenotypes in BBS 4 and 6 null mice consistent with impaired Shh signalling, and knockdown of IFT88 in the human adrenocortical carcinoma cell line H295R affects steroidogenesis. These data support a role for the primary cilium in adrenal development, differentiation and function.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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