AST-1, a novel ETS-box transcription factor, controls axon guidance and pharynx development in C. elegans

Abstract

Neurons send out axons and dendrites over large distances into target areas where they eventually form synapses with selected target cells. Axonal navigation is controlled by a variety of extracellular signals and neurons express receptors only for that subset of signals they need to navigate to their own target area. How the expression of axon guidance receptors is regulated is not understood. In genetic screens for mutants with axon guidance defects, we identified an ETS-domain transcription factor, AST-1, specifically required for axon navigation in certain classes of interneurons. In addition, ast-1 has a role in the differentiation of the ventral cord pioneer neuron AVG. Outside the nervous system, ast-1 is essential for morphogenesis of the pharynx. Ast-1 is transiently expressed in several classes of neurons (including AVG) during neuronal differentiation with a peak expression during late stages of neuronal differentiation and axon outgrowth. Ast-1 genetically interacts with other transcription factors controlling neuronal differentiation like lin-11 and zag-1 as well as components of the netrin pathway suggesting that ast-1 might control the expression of components of the netrin signal transduction machinery.

Genomic and Biochemical Insights into the Specificity of ETS Transcription Factors

“…Genetic studies in C. elegans (19) and Drosophila (20) demonstrate this same trend, with a variety of phenotypes suggesting specialized functions ranging from organ cell fate and neuronal development to oogenesis and aging (Supplemental Table 1) (21–26). Although classic genetics approaches can be limited as a result of potential redundancy within the family, this diversity strongly indicates that different ETS family members carry out distinct biological roles.…”

Gene Expression of Caenorhabditis elegans Neurons Carries Information on Their Synaptic Connectivity

“…The list of 15 genes described in Table S4 (results of the intersection between the prediction and covariation correlation assays) compose our most plausible gene targets for further investigation. Indeed, some of the genes in this list were already identified in previous synaptogenesis studies, such as unc-5, tax-2, tax-4 [24], and lin-11 [25,26]. Yet, some interesting clues indirectly point to the additional involvement of genes from our list that have not been previously known to be directly involved in synaptogenesis: though there is currently no evidence that ceh-23 plays a direct role in axon guidance in C. elegans, although it does play a role in specific cell differentiation, its Drosophila melanogaster homolog, dhb-9, is known to be involved in neural development, axonal pathfinding, and target recognition [27,28].…”

Differentiation of Carbon Dioxide-Sensing Neurons in Caenorhabditis elegans Requires the ETS-5 Transcription Factor

“…Like ets-5, the ast-1 gene is a regulator of neuronal differentiation: ast-1 is required for the terminal differentiation of all dopaminergic neurons (Flames and Hobert 2009). AST-1 also regulates axon guidance in some classes of interneurons (Schmid et al 2006). By contrast, the ets-4 and lin-1 genes are not known to affect neuronal differentiation.…”