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Published March 2004 | public
Journal Article

Characterization of chicken Nf2/merlin indicates regulatory roles in cell proliferation and migration

Abstract

The neurofibromatosis 2 (NF2) tumor suppressor protein merlin, or schwannomin, functions as a negative growth regulator such that inactivating mutations in Nf2 predispose humans to tumors. In addition, merlin has a critical role during embryonic development. Nf2-deficient mice die early during embryogenesis, with defects in gastrulation and extraembryonic tissues. To investigate the function of Nf2/merlin during embryonic development, we first identified the homologous Nf2 gene in chicken (cNf2) and examined the distribution of chicken merlin (c-merlin) during myogenesis. cNf2 encoded a full-length mRNA of 1,770 nucleotides and a protein of 589 residues. C-merlin shared high sequence homology and common protein motifs with vertebrate and Drosophila merlins. In addition, cNF2 functions as a negative growth regulator similar to human and Drosophila merlin in vitro. In vivo, c-merlin was expressed diffusely in the forming dermomyotome but down-regulated in migratory muscle precursors in the forelimb. As muscle formed in the limb, c-merlin expression was up-regulated. As an initial examination of c-merlin function during myogenesis, c-merlin was ectopically expressed in muscle precursors and the effects on muscle development were examined. We show that ectopic merlin expression reduces the proliferation of muscle precursors as well as their ability to migrate effectively in limb mesoderm. Collectively, these results demonstrate that c-merlin is developmentally regulated in migrating and differentiating myogenic cells, where it functions as a negative regulator of both muscle growth and motility.

Additional Information

© 2004 Wiley-Liss, Inc. Received 5 August 2003; Revised 17 October 2003; Accepted 4 November 2003. C.E.K., D.H.G., and M.B.F. received funding by the Muscular Dystrophy Association and the National Institutes of Health. Grant sponsor: Muscular Dystrophy Association; Grant numbers: MH59894; NS35848; Grant sponsor: National Institutes of Health; Grant number: HD15527.

Additional details

Created:
August 22, 2023
Modified:
October 17, 2023