Department of Biological Sciences, University of Illinois at Chicago, IL 60607, USA.
Graduate Program in Neuroscience, University of Illinois at Chicago, IL 60607, USA.
Genetics. 2021 Oct 2;219(2). doi: 10.1093/genetics/iyab133.
General identity of the Caenorhabditis elegans AWC olfactory neuron pair is specified by the OTX/OTD transcription factor CEH-36 and the HMG-box transcription factor SOX-2, followed by asymmetrical differentiation of the pair into two distinct subtypes, default AWCOFF and induced AWCON, through a stochastic signaling event. The HMX/NKX transcription factor MLS-2 regulates the expression of ceh-36 to specify general AWC identity. However, general AWC identity is lost in only one of the two AWC cells in the majority of mls-2 null mutants displaying defective general AWC identity, suggesting that additional transcription factors have a partially overlapping role with MLS-2 in the specification of general AWC identity. Here, we identify a role of unc-62, encoding a homothorax/Meis/TALE homeodomain protein, in the specification of general AWC identity. As in mls-2 null mutants, unc-62 null mutants showed an incomplete penetrance in loss of general AWC identity. However, unc-62; mls-2 double mutants display a nearly complete penetrance of identity loss in both AWC cells. Thus, unc-62 and mls-2 have a partially overlapping function in the specification of general AWC identity. Furthermore, our genetic results suggest that mls-2 and unc-62 act cell autonomously in promoting the AWCON subtype. Together, our findings reveal the sequential roles of the unc-62 and mls-2 pair in AWC development, specification of general AWC identity in early embryogenesis, and asymmetric differentiation of AWC subtypes in late embryogenesis.
秀丽隐杆线虫 AWC 嗅觉神经元对的一般身份由 OTX/OTD 转录因子 CEH-36 和 HMG 盒转录因子 SOX-2 决定，随后通过随机信号事件，该对神经元对不对称地分化为两个不同的亚型，默认的 AWCOFF 和诱导的 AWCON。HMX/NKX 转录因子 MLS-2 调节 ceh-36 的表达以指定一般 AWC 身份。然而，在大多数 MLS-2 缺失突变体中，尽管一般 AWC 身份丧失，但只有两个 AWC 细胞中的一个丧失一般 AWC 身份，这表明其他转录因子在指定一般 AWC 身份方面与 MLS-2 具有部分重叠的作用。在这里，我们确定了编码同源异形盒/Meis/TALE 同源域蛋白的 unc-62 在指定一般 AWC 身份中的作用。与在 mls-2 缺失突变体中一样，unc-62 缺失突变体在丧失一般 AWC 身份方面的不完全穿透性。然而，unc-62;mls-2 双突变体在两个 AWC 细胞中几乎完全丧失了身份丧失的穿透性。因此，unc-62 和 mls-2 在指定一般 AWC 身份方面具有部分重叠的功能。此外，我们的遗传结果表明，mls-2 和 unc-62 在促进 AWCON 亚型方面具有自主作用。总之，我们的研究结果揭示了 unc-62 和 mls-2 对 AWC 发育、早期胚胎发生中一般 AWC 身份的指定以及晚期胚胎发生中 AWC 亚型的不对称分化的顺序作用。
