RNA helicase A is essential for normal gastrulation
RNA helicase A is essential for normal gastrulation
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DOI：
10.1073/pnas.95.23.13709
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发表时间：
1998-11-10
影响因子：
11.1
通讯作者：
Hurwitz, J
中科院分区：
文献类型：
--
作者：
Lee, CG;Soares, VD;Hurwitz, J
RNA解旋酶A（RHA）是果蝇无雄性蛋白的人类同源物，是雄性果蝇发育的必需因子。最近的研究表明，RHA与cAMP反应元件合作，介导许多基因的cAMP依赖性转录激活。由于cAMP作为第二信使参与了许多信号通路，我们研究了RHA在哺乳动物胚胎发生过程中的功能。为了检查RHA在哺乳动物发育中的作用，通过同源重组产生RHA敲除小鼠。纯合性的突变RHA等位基因导致早期胚胎致死。组织学分析，结合RHA缺失胚胎的末端脱氧核苷酸转移酶介导的UTP末端标记（TUNEL）反应，揭示了在原肠胚形成期间胚胎外胚层细胞中特异性的显著的凋亡性细胞死亡，RNA原位分析了HNF-3 β和Brachyury（原肠胚形成的两种分子标记物）的表达，在第7.5天和第8.5天搁置RHLA缺失胚胎，分别以与胚胎的条纹前期和早期阶段相似的模式表达HNF-3 β和Brachyury，这些观察结果表明，RHA是必要的早期胚胎发育，并建议RHA的胚胎外胚层的生存和分化的要求。
RNA helicase A (RHA) is the human homologue of the Drosophila maleless protein, an essential factor for the development of male flies. Recently, it was shown that RHA cooperates with the cAMP-responsive element in mediating the cAMP-dependent transcriptional activation of a number of genes. Due to the participation of cAMP as a second messenger in a number of signaling pathways, we examined the function of RHA during mammalian embryogenesis. To examine the role(s) of RHA in mammalian development, RHA knockout mice were generated by homologous recombination. Homozygosity for the mutant RHA allele led to early embryonic lethality. Histological analysis, combined with terminal deoxynucleotidyltransferase-mediated UTP end labeling (TUNEL) reactions of RHA-null embryos, revealed marked apoptotic cell death specifically in embryonic ectodermal cells during gastrulation, RNA in situ analyses of the expression of HNF-3 beta and Brachyury, two molecular markers for gastrulation, shelved that RHLA-null embryos at days 7.5 and 8.5 expressed both HNF-3 beta and Brachyury in a pattern similar to those of pre- and early streak stages of embryos, respectively, These observations indicate that RHA is necessary for early embryonic development and suggest the requirement of RHA for the survival and differentiation of embryonic ectoderm.