Cis-regulatory mechanisms of gene expression in an olfactory neuron type in Caenorhabditis elegans.

The generation of cellular diversity is dependent on the precise spatiotemporal regulation of gene expression by both cis- and trans-acting mechanisms. The developmental principles regulating expression of specific gene subsets in individual cell types are not fully understood. Here we define the cis-regulatory mechanisms driving expression of cell-selective and broadly expressed genes in vivo in the AWB olfactory neuron subtype in C. elegans. We identify an element that is necessary to drive expression of neuron-selective chemoreceptor genes in the AWB neurons, and show that this element functions in a context-dependent manner. We find that the expression of broadly expressed sensory neuronal genes in the AWB neurons is regulated by diverse cis- and trans-regulatory mechanisms that act partly in parallel to the pathways governing expression of AWB-selective genes. We further demonstrate that cis-acting mechanisms driving gene expression in the AWB neurons appear to have diverged in related nematode species. Our results provide insights into the cis-regulatory logic driving cell-specific gene expression, and suggest that variations in this logic contribute to the generation of functional diversity.

BDNF and CNTF regulate cholinergic properties of sympathetic neurons through independent mechanisms.

Cultured neonatal sympathetic neurons can synthesize and corelease norepinephrine (NE) and acetylcholine (ACh). Evoked release of NE has an excitatory effect on the beat rate of cocultured cardiac myocytes while ACh release results in myocyte inhibition. Here we show that the cholinergic properties of the neurons and the relative level of NE and ACh corelease are modulated by neurotrophic factors. Brain-derived neurotrophic factor (BDNF) rapidly promoted ACh release in the absence of cholinergic differentiation activity and even in neurons that were predominantly noradrenergic. This increase in the cholinergic component of sympathetic cotransmission was sufficient for myocytes to display an overall inhibitory response to neuronal stimulation. In contrast, short-term growth in ciliary neurotrophic factor (CNTF) resulted in the upregulation of cholinergic and downregulation of noradrenergic markers without an effect on normal excitatory neurotransmission. Only once the cells had acquired a cholinergic phenotype did CNTF acutely promote the evoked release of the cholinergic vesicle pool. The results of this study indicate that BDNF and CNTF, acting through independent pathways, modulate NE and ACh cotransmission to regulate the level of sympathetic excitation or inhibition of cardiac myocytes.