Hmx3a Has Essential Functions in Zebrafish Spinal Cord, Ear and Lateral Line Development.

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 subfamily 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 () and are coexpressed in spinal dI2 and V1 interneurons, whereas , , and are not expressed in spinal cord. Using mutational analyses, we demonstrate that, in addition to its previously reported role in ear development, 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 and during embryonic development, zebrafish mutants are viable and have no obviously abnormal phenotypes in sensory structures or neurons that require In addition, embryos homozygous for deletions of both and have identical phenotypes to severe single mutants. However, mutating in hypomorphic mutants that usually develop normally, results in abnormal ear and lateral line phenotypes. This suggests that while cannot compensate for loss of , it does function in these developmental processes, although to a much lesser extent than More surprisingly, our mutational analyses suggest that Hmx3a may not require its homeodomain DNA-binding domain for its roles in viability or embryonic development.