Singhvi Aakanksha, Frank C Andrew, Garriga Gian
Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA.
Genetics. 2008 Jun;179(2):887-98. doi: 10.1534/genetics.108.088948. Epub 2008 May 27.
Understanding how neurons adopt particular fates is a fundamental challenge in developmental neurobiology. To address this issue, we have been studying a Caenorhabditis elegans lineage that produces the HSN motor neuron and the PHB sensory neuron, sister cells produced by the HSN/PHB precursor. We have previously shown that the novel protein HAM-1 controls the asymmetric neuroblast division in this lineage. In this study we examine tbx-2 and egl-5, genes that act in concert with ham-1 to regulate HSN and PHB fate. In screens for mutants with abnormal HSN development, we identified the T-box protein TBX-2 as being important for both HSN and PHB differentiation. TBX-2, along with HAM-1, regulates the migrations of the HSNs and prevents the PHB neurons from adopting an apoptotic fate. The homeobox gene egl-5 has been shown to regulate the migration and later differentiation of the HSN. While mutations that disrupt its function show no obvious role for EGL-5 in PHB development, loss of egl-5 in a ham-1 mutant background leads to PHB differentiation defects. Expression of EGL-5 in the HSN/PHB precursor but not in the PHB neuron suggests that EGL-5 specifies precursor fate. These observations reveal a role for both EGL-5 and TBX-2 in neural fate specification in the HSN/PHB lineage.
了解神经元如何获得特定命运是发育神经生物学中的一项基本挑战。为了解决这个问题，我们一直在研究秀丽隐杆线虫的一个细胞谱系，该谱系产生HSN运动神经元和PHB感觉神经元，它们是由HSN/PHB前体细胞产生的姐妹细胞。我们之前已经表明，新型蛋白质HAM-1控制该谱系中神经母细胞的不对称分裂。在这项研究中，我们研究了tbx-2和egl-5，这两个基因与ham-1协同作用来调节HSN和PHB的命运。在筛选HSN发育异常的突变体时，我们发现T盒蛋白TBX-2对HSN和PHB的分化都很重要。TBX-2与HAM-1一起调节HSN的迁移，并防止PHB神经元走向凋亡命运。同源盒基因egl-5已被证明可调节HSN的迁移和后期分化。虽然破坏其功能的突变在PHB发育中未显示出EGL-5有明显作用，但在ham-1突变背景下egl-5的缺失会导致PHB分化缺陷。EGL-5在HSN/PHB前体细胞中表达，但在PHB神经元中不表达，这表明EGL-5决定前体细胞的命运。这些观察结果揭示了EGL-5和TBX-2在HSN/PHB谱系神经命运特化中的作用。
