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Originally published as MBC in Press, 10.1091/mbc.E07-08-0782 on February 13, 2008

Vol. 19, Issue 4, 1575-1586, April 2008

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SoxE Proteins Are Differentially Required in Mouse Adrenal Gland Development

Simone Reiprich*, C. Claus Stolt*, Silke Schreiner*, Rosanna Parlato{dagger}, and Michael Wegner*

*Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg, D-91054 Erlangen, Germany; and {dagger}Department of Molecular Biology of the Cell I, German Cancer Research Center, D-69120 Heidelberg, Germany

Submitted August 13, 2007; Revised January 22, 2008; Accepted February 5, 2008
Monitoring Editor: Marianne Bronner-Fraser

Sry-box (Sox)8, Sox9, and Sox10 are all strongly expressed in the neural crest. Here, we studied the influence of these closely related transcription factors on the developing adrenal medulla as one prominent neural crest derivative. Whereas Sox9 was not expressed, both Sox8 and Sox10 occurred widely in neural crest cells migrating to the adrenal gland and in the gland itself, and they were down-regulated in cells expressing catecholaminergic traits. Sox10-deficient mice lacked an adrenal medulla. The adrenal anlage was never colonized by neural crest cells, which failed to specify properly at the dorsal aorta and died apoptotically during migration. Furthermore, mutant neural crest cells did not express Sox8. Strong adrenal phenotypes were also observed when the Sox10 dimerization domain was inactivated or when a transactivation domain in the central portion was deleted. Sox8 in contrast had only minimal influence on adrenal gland development. Phenotypic consequences became only visible in Sox8-deficient mice upon additional deletion of one Sox10 allele. Replacement of Sox10 by Sox8, however, led to significant rescue of the adrenal medulla, indicating that functional differences between the two related Sox proteins contribute less to the different adrenal phenotypes of the null mutants than dependence of Sox8 expression on Sox10.


This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-08-0782) on February 13, 2008.

Address correspondence to: Michael Wegner (m.wegner{at}biochem.uni-erlangen.de)

Abbreviations used: β-HSD, β-hydroxysteroid-dehydrogenase; DBH, dopamine-β-hydroxylase; dpc, days postcoitum; Mash1, mammalian achaete scute homologue 1; Phox2b, paired homeobox 2b; PNMT, phenylethanolamine N-methyltransferase; SF1, steroidogenic factor 1; Sox, Sry-box; TH, tyrosine hydroxylase; TUNEL, terminal deoxynucleotidyl transferase dUTP nick-end labeling; VMAT, vesicular monoamine transporter.







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