Identification of spatial and temporal cues that regulate postembryonic expression of axon maintenance factors in theC. elegansventral nerve cord

Abstract

Patterns of gene expression are under precise spatial and temporal control. A particularly striking example is represented by several members of thezig gene family, which code for secreted immunoglobulin domain proteins required for maintaining ventral nerve cord organization inCaenorhabditis elegans. These genes are coordinately expressed in a single interneuron in the ventral nerve cord, known as PVT. Their expression is initiated at a precise postembryonic stage, long after PVT has been generated in mid-embryogenesis. We define spatial and temporal cues that are required for the precise regulation of zig gene expression. We find that two LIM homeobox genes, the Lhx3-class gene ceh-14 and the Lmx-class gene lim-6 are coordinately required for ziggene expression in PVT. Temporal control of zig gene expression is conferred by the heterochronic gene lin-14, a nuclear factor previously implicated in developmental timing in various contexts. Loss of thelim-6 and ceh-14 transcription factors and the developmental timer lin-14 cause not only a loss of zig gene expression but also lead to defects in the maintenance of ventral nerve cord architecture. Overriding the normal spatiotemporal control of ziggene expression through expression of one of the zig genes under control of heterologous promoters also causes axon patterning defects in the ventral nerve cord. Our findings illustrate the importance of spatial and temporal control of gene expression in the nervous system and, furthermore,implicate heterochronic genes in postmitotic neural patterning events.

The Small, Secreted Immunoglobulin Protein ZIG-3 Maintains Axon Position in Caenorhabditis elegans

“…(B) Quantification of rescue data. Note that we have previously shown that overexpression of zig-4, using again the myo-3 promoter, causes PVQ axon outgrowth defects (Aurelio et al 2003). In the experiments shown here myo-3Tzig-4 was injected at lower concentration, which did not result in axon outgrowth defects.…”

The AHR-1 aryl hydrocarbon receptor and its co-factor the AHA-1 aryl hydrocarbon receptor nuclear translocator specify GABAergic neuron cell fate inC. elegans

“…It has been reported that in lim-6 mutants Pglr-1GFP expression is normal and RMEL/R neurons are normal , indicating that the effect on Pglr-1GFP in ahr-1(ju145) animals is independent of lim-6. In addition, we found that the expression of a transgene Punc-47sGFP that contains a shortened unc-47 promoter, and which is expressed specifically in RMEL/R but not in RMED/V (Aurelio et al, 2003), was abolished in RMEL/R neurons of ahr-1(ju145) animals (Fig. 3G,H).…”

“…Genetic nomenclature follows the standard C. elegans system (Horvitz et al, 1979). The GFP reporter strains used are listed below: juIs76 (Punc-25GFP) (Huang et al, 2002), juIs1 (Punc-25SNB-1-GFP) (Zhen and Jin, 1999), oxIs12 (Punc-47flGFP) (McIntire et al, 1997), otIs37 (Punc-47sGFP) (Aurelio et al, 2003), nuIs25 (Pglr-1GFP) (Hart et al, 1995), otEx406 (Plim-6rGFP) , juEx517 (Pavr-15GFP) (Dent et al, 1997) (this study), vbEx1 (Pclh-6GFP) (Bianchi et al, 2001), iaIs2 (AHR-1::GFP) (Qin, H and J.A.P.-C., unpublished). ZG69 aha-1(ia1); iaEx28 was used as the starting strain to examine the role of aha-1 in RME neurons.…”

β-Spectrin functions independently of Ankyrin to regulate the establishment and maintenance of axon connections in theDrosophilaembryonic CNS

“…Our observations support the idea that some level of Slit/Robo repulsion is required continuously to keep ipsilateral axons on their own side of the midline. A more dramatic example of pathway maintenance has been described in C. elegans, where mutations in the Zig genes lead to a 'flipping' of axon pathways over the midline (Aurelio et al, 2003;Aurelio et al, 2002). Additionally, in Drosophila, it has been shown that ␤-Spectrin is essential for synapse stabilization (Pielage et al, 2005).…”