Unc-86 encodes a class IV POU domain transcription factor involved in neuronal development. Mutant phenotypes include egg-laying, mechanosensation, chemotaxis, thermotaxis defects and uncoordinated movement, attributing to the central role of
unc-86 in the alteration of cell lineage and differentiation. Since the consequences of
unc-86 mutations are so different in cell types of non-related lineages,
unc-86 has to target distinct sets of downstream genes in these lineages. In order to characterize the transcription activation properties of UNC-86 we have mapped the activation domains of UNC-86. Members of the POU protein family are known to associate with a variety of other proteins on DNA to achieve specific gene expression. By screening for interacting proteins of UNC-86 in various yeast systems we are elucidating how UNC-86 achieves its differential activity in distinct neural cell types. We will be presenting current results of these screens. The mammalian genes of the Brn-3 subfamily, Brn-3a, Brn-3b, and Brn-3c, constitute other members of the class IV POU domain family and appear to be orthologues of the nematode gene
unc-86. Targeted deletions of the Brn-3 genes in mice produce animals with altered suckling behavior, loss of most retinal ganglions and complete deafness due to missing hair cells in the inner ear, respectively. While the phenotypes ascertain a distinct role of the Brn-3 genes in the development of auditory, visual and somatosensory systems, the sequence-homologies, similar DNA-binding specificities, and the overlapping expression patterns indicate a partial functional redundancy of the Brn-3 genes. Thus, it has been postulated that despite differences in organ structure, signal transduction, and information processing the above mentioned neuronal systems exhibit homologous transcriptional regulatory mechanisms in development. In order to further elucidate the functional aspects of the orthologies between the nematode and the mammalian genes several approaches are implemented.