Brn3/POU-IV-type POU homeobox genes-Paradigmatic regulators of neuronal identity across phylogeny.

Abstract

One approach to understand the construction of complex systems is to investigate whether there are simple design principles that are commonly used in building such a system. In the context of nervous system development, one may ask whether the generation of its highly diverse sets of constituents, that is, distinct neuronal cell types, relies on genetic mechanisms that share specific common features. Specifically, are there common patterns in the function of regulatory genes across different neuron types and are those regulatory mechanisms not only used in different parts of one nervous system, but are they conserved across animal phylogeny? We address these questions here by focusing on one specific, highly conserved and well-studied regulatory factor, the POU homeodomain transcription factor UNC-86. Work over the last 30 years has revealed a common and paradigmatic theme of unc-86 function throughout most of the neuron types in which Caenorhabditis elegans unc-86 is expressed. Apart from its role in preventing lineage reiterations during development, UNC-86 operates in combination with distinct partner proteins to initiate and maintain terminal differentiation programs, by coregulating a vast array of functionally distinct identity determinants of specific neuron types. Mouse orthologs of unc-86, the Brn3 genes, have been shown to fulfill a similar function in initiating and maintaining neuronal identity in specific parts of the mouse brain and similar functions appear to be carried out by the sole Drosophila ortholog, Acj6. The terminal selector function of UNC-86 in many different neuron types provides a paradigm for neuronal identity regulation across phylogeny. This article is categorized under: Gene Expression and Transcriptional Hierarchies > Regulatory Mechanisms Invertebrate Organogenesis > Worms Nervous System Development > Vertebrates: Regional Development.