The C. elegans nuclear receptor gene fax-1 and homeobox gene unc-42 coordinate interneuron identity by regulating the expression of glutamate receptor subunits and other neuron-specific genes

Abstract

The fax-1 gene of the nematode C. elegans encodes a conserved nuclear receptor that is the ortholog of the human PNR gene and functions in the specification of neuron identities. Mutations in fax-1 result in locomotion defects. FAX-1 protein accumulates in the nuclei of 18 neurons, among them the AVA, AVB, and AVE interneuron pairs that coordinate body movements. The identities of AVA and AVE interneurons are defective in fax-1 mutants; neither neuron expresses the NMDA receptor subunits nmr-1 and nmr-2. Other ionotropic glutamate receptor subunits are expressed normally in the AVA and AVE neurons. The unc-42 homeobox gene also regulates AVA and AVE identity; however, unc-42 mutants display the complementary phenotype: NMDA receptor subunit expression is normal, but some non-NMDA glutamate receptor subunits are not expressed. These observations support a combinatorial role for fax-1 and unc-42 in specifying AVA and AVE identity. However, in four other neuron types, fax-1 is regulated by unc-42, and both transcriptional regulators function in the regulation of the opt-3 gene in the AVE neurons and the flp-1 and ncs-1 genes in the AVK neurons. Therefore, while fax-1 and unc-42 act in complementary parallel pathways in some cells, they function in overlapping or linear pathways in other cellular contexts, suggesting that combinatorial relationships among transcriptional regulators are complex and cannot be generalized from one neuron type to another.

The unfulfilled/DHR51 gene of Drosophila melanogaster modulates wing expansion and fertility

“…This broader expression of unf is similar to the expression of fax-1 in C. elegans (Much et al, 2000;Wightman et al, 2005).…”

“…Expression of the Drosophila gene dsf is also limited to a subset of neurons in the brain, is required for male and female courtship behavior, and functions as a transcriptional repressor (Finley et al, 1997(Finley et al, , 1998Pitman et al, 2002). The fax-1 gene of C. elegans is expressed in approximately 18 neurons and in a small number of cells of the somatic gonad and vulva (Much et al, 2000;Wightman et al, 2005), is required for coordinated locomotion (Wightman et al, 1997), and regulates the expression of presynaptic and postsynaptic products (Wightman et al, 2005). Neurons lacking fax-1 typically exhibit axon pathfinding defects (Wightman et al, 1997(Wightman et al, , 2005Much et al, 2000).…”

“…The fax-1 gene of C. elegans is expressed in approximately 18 neurons and in a small number of cells of the somatic gonad and vulva (Much et al, 2000;Wightman et al, 2005), is required for coordinated locomotion (Wightman et al, 1997), and regulates the expression of presynaptic and postsynaptic products (Wightman et al, 2005). Neurons lacking fax-1 typically exhibit axon pathfinding defects (Wightman et al, 1997(Wightman et al, , 2005Much et al, 2000). PNR, the vertebrate ortholog of fax-1 (Bertrand et al, 2004;DeMeo et al, 2008) provides one of the most extreme examples of spatial restriction of all nuclear receptors.…”

TheC. elegansTailless/TLX transcription factornhr-67controls neuronal identity and left/right asymmetric fate diversification

“…A nuclear receptor closely related to NHR-67, FAX-1, also controls neuronal identity and morphology in C. elegans (Much et al, 2000;Wightman et al, 2005). Similarly, its vertebrate homolog, PNR, promotes proper photoreceptor cell fate specification (Haider et al, 2000).…”

Nuclear receptors in nematode development: Natural experiments made by a phylum

“…FAX-1 functions in the specification of neuron identity. It regulates the path-finding of axons that extend along the ventral nerve cord and axons in the nerve ring and is required for normal neurotransmitter expression [105][106][107]. FAX-1 protein accumulates in the nuclei of 18 neurons (AVA, AVB, and AVE interneuron pairs) that coordinate body movements.…”