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Dev Biol 2011 Mar 01;3511:135-45. doi: 10.1016/j.ydbio.2010.12.043.
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Functional analysis of Rfx6 and mutant variants associated with neonatal diabetes.

Mutations in rfx6 were recently associated with Mitchell-Riley syndrome, which involves neonatal diabetes, and other digestive system defects. To better define the function of Rfx6 in early endoderm development we cloned the Xenopus homologue. Expression of rfx6 begins early, showing broad expression throughout the anterior endoderm; at later stages rfx6 expression becomes restricted to the endocrine cells of the gut and pancreas. Morpholino knockdown of rfx6 caused a loss of pancreas marker expression, as well as other abnormalities. Co-injection of exogenous wild-type rfx6 rescued the morpholino phenotype in Xenopus tadpoles, whereas attempts to rescue the loss-of-function phenotype using mutant rfx6 based on Mitchell-Riley patients were unsuccessful. To better define the pleiotropic effects, we performed microarray analyses of gene expression in knockdown foregut tissue. In addition to pancreatic defects, the microarray analyses revealed downregulation of lung, stomach and heart markers and an upregulation of kidney markers. We verified these results using RT-PCR and in situ hybridization. Based on the different rfx6 expression patterns and our functional analyses, we propose that rfx6 has both early and late functions. In early development Rfx6 plays a broad role, being essential for development of most anterior endodermal organs. At later stages however, Rfx6 function is restricted to endocrine cells.

PubMed ID: 21215266
PMC ID: PMC3042741
Article link: Dev Biol
Grant support: [+]

Species referenced: Xenopus
Genes referenced: agr2 cela1.2 cela1.6 foxa2 gcg hhex ins kcnj1 neurod1 nkx2-5 onecut1 pdx1 ptf1a rfx6 sfrp5 sftpc sox17a sst.1
Morpholinos: rfx6 MO1 rfx6 MO2

GEO Series: GSE23642: NCBI

Article Images: [+] show captions
External Resources:

References [+] :
Aftab, Identification and characterization of novel human tissue-specific RFX transcription factors. 2008, Pubmed