Transcription factors that contain a homeodomain DNA-binding domain have crucial functions in most aspects of cellular function and embryonic development in both animals and plants. Hmx proteins are a sub-family of NK homeodomain-containing proteins that have fundamental roles in development of sensory structures such as the eye and the ear. However, Hmx functions in spinal cord development have not been analyzed. Here we show that zebrafish (Danio rerio) hmx2 and hmx3a are co-expressed in spinal dI2 and V1 interneurons, whereas hmx3b, hmx1 and hmx4 are not expressed in spinal cord. Using mutational analyses, we demonstrate that, in addition to its previously reported role in ear development, hmx3a is required for correct specification of a subset of spinal interneuron neurotransmitter phenotypes, as well as correct lateral line progression and survival to adulthood. Surprisingly, despite similar expression patterns of hmx2 and hmx3a during embryonic development, zebrafish hmx2 mutants are viable and have no obviously abnormal phenotypes in sensory structures or neurons that require hmx3a. In addition, embryos homozygous for deletions of both hmx2 and hmx3a have identical phenotypes to severe hmx3a single mutants. However, mutating hmx2 in hypomorphic hmx3a mutants that usually develop normally, results in abnormal ear and lateral line phenotypes. This suggests that while hmx2 cannot compensate for loss of hmx3a, it does function in these developmental processes, although to a much lesser extent than hmx3a. More surprisingly, our mutational analyses suggest that Hmx3a may not require its homeodomain DNA-binding domain for its roles in viability or embryonic development.

中文翻译：

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Hmx3a在斑马鱼脊髓，耳朵和侧线发育中具有重要功能。

包含同源域DNA结合域的转录因子在动物和植物的细胞功能和胚胎发育的大多数方面都具有至关重要的功能。Hmx蛋白是含NK同源结构域的蛋白的一个亚家族，在诸如眼睛和耳朵的感觉结构的发育中具有基本作用。但是，尚未分析Hmx在脊髓发育中的功能。在这里，我们显示斑马鱼（Danio rerio）hmx2和hmx3a在脊髓dI2和V1中神经元中共表达，而hmx3b，hmx1和hmx4在脊髓中不表达。使用突变分析，我们证明，除了先前报道的其在耳朵发育中的作用外，hmx3a还需要正确指定一部分脊髓神经元神经递质表型，以及正确的侧线进展和成年生存率。令人惊讶的是，尽管在胚胎发育过程中hmx2和hmx3a的表达模式相似，但斑马鱼hmx2突变体是可行的，并且在需要hmx3a的感觉结构或神经元中没有明显的异常表型。此外，纯合的hmx2和hmx3a缺失的胚胎具有与严重的hmx3a单突变体相同的表型。但是，通常发育正常的亚型hmx3a突变体中的hmx2突变会导致耳朵和侧线表型异常。这表明，虽然hmx2无法补偿hmx3a的损失，但它在这些发育过程中确实起作用，尽管程度要比hmx3a小得多。更令人惊讶的是