The Caenorhabditis elegans gene ham-2 links Hox patterning to migration of the HSN motor neuron
The Caenorhabditis elegans gene ham-2 links Hox patterning to migration of the HSN motor neuron
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DOI：
10.1101/gad.13.4.472
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发表时间：
1999-02-15
影响因子：
10.5
通讯作者：
Garriga, G
中科院分区：
文献类型：
--
作者：
Baum, PD;Guenther, C;Garriga, G
秀丽线虫HSN运动神经元允许在单细胞分辨率下对神经元发育进行遗传分析。胚胎后部的EGL-5 HOX基因是HSN早期(胚胎)和晚期(幼体)发育所必需的。在这里，我们表明，HAM-2编码一个锌指蛋白，作用于EGL-5下游，指导HSN细胞迁移，这是一种早期分化事件。我们还证明了EGL-43锌指蛋白，也是HSN迁移所必需的，在HSN迁移过程中特异地在HSN中表达。在EGL-5突变背景下，HSN仍然表达EGL-43，但在细胞迁移结束时表达不再下调。最后，我们发现了UNC-86在HSN早期分化中的新作用，UNC-86是一种POU同源结构域转录因子，以前被证明在EGL-5下游调节HSN晚期分化。在UNC-86；HAM-2双突变体中，HSN在EGL-43下调方面存在缺陷，这是一种EGL-5样的表型，在两个单一突变体中都不存在。因此，在HSN中，Hox基因EGL-5通过激活编码转录因子Ham-2和UNC-86的基因的转录来调节细胞命运，这些转录因子依次单独控制一些分化事件，并联合影响其他分化事件。
The Caenorhabditis elegans HSN motor neurons permit genetic analysis of neuronal development at single-cell resolution. The egl-5 Hox gene, which patterns the posterior of the embryo, is required for both early (embryonic) and late (larval) development of the HSN. Here we show that ham-2 encodes a zinc finger protein that acts downstream of egl-5 to direct HSN cell migration, an early differentiation event. We also demonstrate that the EGL-43 zinc finger protein, also required for HSN migration, is expressed in the HSN specifically during its migration. In an egl-5 mutant background, the HSN still expresses EGL-43, but expression is no longer down-regulated at the end of the cell's migration. Finally, we find a new role in early HSN differentiation for UNC-86, a POU homeodomain transcription factor shown previously to act downstream of egl-5 in the regulation of late HSN differentiation. In an unc-86; ham-2 double mutant the HSNs are defective in EGL-43 down-regulation, an egl-5-like phenotype that is absent in either single mutant. Thus, in the HSN, a Hox gene, egl-5, regulates cell fate by activating the transcription of genes encoding the transcription factors HAM-2 and UNC-86 that in turn individually control some differentiation events and combinatorially affect others.