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Molecular and Cellular Biology, April 2009, p. 2129-2138, Vol. 29, No. 8
0270-7306/09/$08.00+0     doi:10.1128/MCB.01644-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

MFng Is Dispensable for Mouse Pancreas Development and Function{triangledown} ,{dagger}

Per Svensson, Ingela Bergqvist,{ddagger} Stefan Norlin,* and Helena Edlund*

Umeå Center for Molecular Medicine, Umeå University, SE-901 87 Umeå, Sweden

Received 22 October 2008/ Returned for modification 12 December 2008/ Accepted 4 February 2009

Notch signaling regulates pancreatic cell differentiation, and mutations of various Notch signaling components result in perturbed pancreas development. Members of the Fringe family of β1,3-N-acetylglucosaminyltransferases, Manic Fringe (MFng), Lunatic Fringe (LFng), and Radical Fringe (RFng), modulate Notch signaling, and MFng has been suggested to regulate pancreatic endocrine cell differentiation. We have characterized the expression of the three mouse Fringe genes in the developing mouse pancreas between embryonic days 9 and 14 and show that the expression of MFng colocalized with the proendocrine transcription factor Ngn3. In contrast, the expression of LFng colocalized with the exocrine marker Ptf1a, whereas RFng was not expressed. Moreover, we show that expression of MFng is lost in Ngn3 mutant mice, providing evidence that MFng is genetically downstream of Ngn3. Gain- and loss-of-function analyses of MFng by the generation of mice that overexpress MFng in early pancreatic progenitor cells and mice with a targeted deletion of MFng provide, however, evidence that MFng is dispensable for pancreas development and function, since no pancreatic defects in these mice were observed.


* Corresponding author. Mailing address: Umeå Center for Molecular Medicine, Umeå University, SE-901 87 Umeå, Sweden. Phone: (46) 090-785 44 29. Fax: (46) 090-785 44 00. E-mail for Helena Edlund: helena.edlund{at}ucmm.umu.se. E-mail for Stefan Norlin: stefan.norlin{at}ucmm.umu.se

{triangledown} Published ahead of print on 17 February 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: Betagenon AB, Box 7966, SE-907 19 Umeå, Sweden.


Molecular and Cellular Biology, April 2009, p. 2129-2138, Vol. 29, No. 8
0270-7306/09/$08.00+0     doi:10.1128/MCB.01644-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.