Characterization of chicken Nf2/merlin indicates regulatory roles in cell proliferation and migration.
Characterization of chicken Nf2/merlin indicates regulatory roles in cell proliferation and migration.
复制标题
鸡 Nf2/merlin 的表征表明其在细胞增殖和迁移中的调节作用。
DOI：
10.1002/dvdy.20002
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Krull,CE
中科院分区：
文献类型：
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作者：
Chen,Y;Gutmann,DH;Haipek,CA;Martinsen,BJ;Bronner-Fraser,M;Krull,CE
神经纤维瘤病2 （NF2）肿瘤抑制蛋白梅林，或神经鞘蛋白，作为一种负生长调节剂，使NF2突变失活，使人类易患肿瘤。此外，梅林在胚胎发育过程中起着关键作用。Nf2缺失小鼠在胚胎发生过程中死亡较早，并伴有原肠胚形成和胚胎外组织缺陷。为了研究nf2 /merlin在胚胎发育过程中的功能，我们首先在鸡中鉴定了同源的nf2基因（cNf2），并检测了鸡梅林（c‐merlin）在肌肉形成过程中的分布。cnf2编码1770个核苷酸的全长mRNA和589个残基的蛋白。C‐merlin与脊椎动物和果蝇amerlins具有高度的序列同源性和共同的蛋白基序。此外，cnf2在体外作为负生长调节剂的功能类似于人类和果蝇amerlin。在体内，c - merlin在形成的真皮组织中广泛表达，但在前肢的移行肌前体中表达下调。随着肢体肌肉的形成，c - merlin的表达上调。作为对c - merlin在肌肉发生过程中功能的初步研究，c - merlin在肌肉前体中异位表达，并对肌肉发育的影响进行了研究。我们发现异位梅林的表达减少了肌肉前体的增殖以及它们在肢体中胚层中有效迁移的能力。总的来说，这些结果表明c - merlin在迁移和分化肌源性细胞中受到发育调节，在那里它作为肌肉生长和运动的负调节因子发挥作用。科学进展，2004(2):541 - 554。©2004 Wiley‐Liss, Inc。
The neurofibromatosis 2 (NF2) tumor suppressor protein merlin, or schwannomin, functions as a negative growth regulator such that inactivating mutations inNf2predispose 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 ofNf2/merlin during embryonic development, we first identified the homologousNf2gene in chicken (cNf2) and examined the distribution of chicken merlin (c‐merlin) during myogenesis.cNf2encoded 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 andDrosophilamerlins. In addition,cNF2functions as a negative growth regulator similar to human andDrosophilamerlin 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. Developmental Dynamics 229:541–554, 2004. © 2004 Wiley‐Liss, Inc.