A Question of Identity: Genes that Distinguish Motoneurons from Interneurons
Van Ryswyk, Liesl
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Van Ryswyk, Liesl
The question of how a single cell can grow, divide, and ultimately acquire a distinct function within an adult animal is central to the field of developmental biology. An elegant way to address this question is by studying the specification of a specific cell type, for example, vertebrate motoneurons. For an animal to be able to move and behave appropriately, individual motoneurons (MNs) must correctly innervate specific muscles. For this to happen, MNs must first be specified and then must differentiate into distinct subtypes, each of which is classified in part by the muscle it innervates. MN subtype specification is dependent on both the acquisition of MN-specific characteristics as well as the failure to acquire characteristics specific to interneurons, cells that only innervate other neurons. The entire process of specification is initiated in progenitor cells and relies on the correct spatial and temporal expression of specific genes. Previous work in various vertebrate models has identified some of the key genes involved in MN specification, most notably transcription factors such as olig2, nkx6s, lhxs, mnxs, and islet1. In this dissertation, I use the zebrafish model to demonstrate novel roles in MN specification for two of these families of transcription factors - the lhxs and the mnxs. I provide evidence that both lhx3 and lhx4 are necessary for normal MN and ventral interneuron (IN) development and work by preventing MNs from expressing IN-specific characteristics. I also show that mnx1, mnx2a, and mnx2b are necessary in MNs both to promote the acquisition of some MN subtype-specific characteristics and to prevent the acquisition of some IN-specific characteristics and appear to be working in part through interactions with islet1. Finally, I identify an intermediate filament gene, inab, as being expressed in a subset of zebrafish MNs and a ventral IN and as having a potential role in the axon outgrowth of a specific MN subtype. Together, this work provides evidence for a mechanism of MN specification dependent on the expression of genes that both promote aspects of MN fate and inhibit aspects of IN fate. This dissertation includes previously unpublished co-authored material.