Neuropeptides

Li, Chris

doi:10.1895/wormbook.1.142.1

Cited by 230 publications

(257 citation statements)

References 116 publications

Supporting

Mentioning

254

Contrasting

Unclassified

Order By: Relevance

“…The HSNs are known to express several neuropeptides and the machinery involved in neuropeptide release (Li and Kim 2008). Specifically, we examined expression of the ida-1 gene, a phosphatase that is involved in neuropeptidergic dense core vesicle biology (Zahn et al 2001).…”

Section: Phenotypic Analysis Of Ham-3 Mutants Reveals Neuronal Defectsmentioning

confidence: 99%

The SWI/SNF Chromatin Remodeling Complex Selectively Affects Multiple Aspects of Serotonergic Neuron Differentiation

et al. 2013

View full text Add to dashboard Cite

Regulatory programs that control the specification of serotonergic neurons have been investigated by genetic mutant screens in the nematode Caenorhabditis elegans. Loss of a previously uncloned gene, ham-3, affects migration and serotonin antibody staining of the hermaphrodite-specific neuron (HSN) pair. We characterize these defects here in more detail, showing that the defects in serotonin antibody staining are paralleled by a loss of the transcription of all genes involved in serotonin synthesis and transport. This loss is specific to the HSN class as other serotonergic neurons appear to differentiate normally in ham-3 null mutants. Besides failing to migrate appropriately, the HSNs also display axon pathfinding defects in ham-3 mutants. However, the HSNs are still generated and express a subset of their terminal differentiation features in ham-3 null mutants, demonstrating that ham-3 is a specific regulator of select features of the HSNs. We show that ham-3 codes for the C. elegans ortholog of human BAF60, Drosophila Bap60, and yeast Swp73/Rsc6, which are subunits of the yeast SWI/SNF and vertebrate BAF chromatin remodeling complex. We show that the effect of ham-3 on serotonergic fate can be explained by ham-3 regulating the expression of the Spalt/SALL-type Zn finger transcription factor sem-4, a previously identified regulator of serotonin expression in HSNs and of the ham-2 Zn transcription factor, a previously identified regulator of HSN migration and axon outgrowth. Our findings provide the first evidence for the involvement of the BAF complex in the acquisition of terminal neuronal identity and constitute genetic proof by germline knockout that a BAF complex component can have cell-type-specific roles during development. N EURONS that express the neurotransmitter serotonin fulfill a number of critical functions in all nervous systems examined to date. In vertebrates, serotonergic neurons modulate anxiety, cognitive processes, mood, body temperature, sleep, sexual behavior, appetite, and metabolism, and their dysfunction has been connected to a variety of human disorders (Muller and Jacobs 2010). In the hermaphroditic Caenorhabditis elegans nervous system, serotonin also controls a number of distinct behaviors (Schafer 2005;Chase and Koelle 2007). Serotonin is utilized as a neurotransmitter under normal conditions by seven neuron types, the sensory neuron ADF; the interneurons AIM and RIH; the motor neurons hermaphroditespecific neurons (HSNs), the ventral cord motor neurons VC4 and VC5; and the neurosecretory NSM cells (Schafer 2005;Chase and Koelle 2007). Under stress conditions, serotonin is used by an additional neuron type, ASG (Pocock and Hobert 2010). One of the serotonergic neurons, the hermaphrodite-specific motor neuron, HSN, utilizes serotonin to signal to vulval muscles to control egg-laying behavior (Schafer 2005). Unlike most other neurons in the C. elegans nervous system, the two bilaterally symmetric HSNs undergo long-range migration. After terminating migration, they extend th...

show abstract

Section: Phenotypic Analysis Of Ham-3 Mutants Reveals Neuronal Defectsmentioning

confidence: 99%

The SWI/SNF Chromatin Remodeling Complex Selectively Affects Multiple Aspects of Serotonergic Neuron Differentiation

et al. 2013

View full text Add to dashboard Cite

show abstract

“…This set of genes consists of the receptor guanylate cyclase gene gcy-9, which is required for the CO 2 -evoked activity of BAG neurons and is a candidate receptor for CO 2 (Hallem et al 2011b); the soluble guanylate cyclase genes gcy-31 and gcy-33, which are required for the O 2 -evoked activity of BAG neurons (Zimmer et al 2009); and the cGMP-gated cation channel genes tax-2 and tax-4, which are required for both the CO 2 -and the O 2 -sensing functions of the BAG neurons (Hallem and Sternberg 2008;Zimmer et al 2009;Hallem et al 2011b). We also examined expression of the BAGexpressed FMRFamide-like neuropeptide genes flp-10 and flp-17, which are involved in the regulation of egg-laying behavior (Li and Kim 2008;Ringstad and Horvitz 2008).…”

Section: Ets-5 Is Required For Normal Bag Neuron Differentiationmentioning

confidence: 99%

“…These results suggest that ets-5 may be the primary transcription factor that regulates expression of the BAG-specific gene battery, whereas more broadly expressed genes may rely on a combinatorial code of transcription factors for expression in BAG neurons. An exception is the flp-10 gene, which is expressed in multiple neurons, functions in multiple neurons besides BAG (Li and Kim 2008;Ringstad and Horvitz 2008), and yet shows greatly reduced expression in the BAG neurons of ets-5 mutants (Figures 4 and 5).…”

Section: Ets-5 Is Required For Normal Bag Neuron Differentiationmentioning

confidence: 99%

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

2011

View full text Add to dashboard Cite

Many animals sense environmental gases such as carbon dioxide and oxygen using specialized populations of gas-sensing neurons. The proper development and function of these neurons is critical for survival, as the inability to respond to changes in ambient carbon dioxide and oxygen levels can result in reduced neural activity and ultimately death. Despite the importance of gas-sensing neurons for survival, little is known about the developmental programs that underlie their formation. Here we identify the ETS-family transcription factor ETS-5 as critical for the normal differentiation of the carbon dioxide-sensing BAG neurons in Caenorhabditis elegans. Whereas wild-type animals show acute behavioral avoidance of carbon dioxide, ets-5 mutant animals do not respond to carbon dioxide. The ets-5 gene is expressed in BAG neurons and is required for the normal expression of the BAG neuron gene battery. ets-5 may also autoregulate its expression in BAG neurons. ets-5 is not required for BAG neuron formation, indicating that it is specifically involved in BAG neuron differentiation and the maintenance of BAG neuron cell fate. Our results demonstrate a novel role for ETS genes in the development and function of gas-detecting sensory neurons.

show abstract

“…Liu et al 2007;Li and Kim 2008). The DCVs in neuroendocrine and PC12 cells are much more abundant and accessible to biochemical and physiological experiments than those in neurons.…”

mentioning

confidence: 99%

A Novel CaM Kinase II Pathway Controls the Location of Neuropeptide Release fromCaenorhabditis elegansMotor Neurons

Hoover

Edwards

et al. 2014

Genetics

View full text Add to dashboard Cite

Neurons release neuropeptides via the regulated exocytosis of dense core vesicles (DCVs) to evoke or modulate behaviors. We found that Caenorhabditis elegans motor neurons send most of their DCVs to axons, leaving very few in the cell somas. How neurons maintain this skewed distribution and the extent to which it can be altered to control DCV numbers in axons or to drive release from somas for different behavioral impacts is unknown. Using a forward genetic screen, we identified loss-of-function mutations in UNC-43 (CaM kinase II) that reduce axonal DCV levels by 90% and cell soma/dendrite DCV levels by 80%, leaving small synaptic vesicles largely unaffected. Blocking regulated secretion in unc-43 mutants restored near wild-type axonal levels of DCVs. Time-lapse video microscopy showed no role for CaM kinase II in the transport of DCVs from cell somas to axons. In vivo secretion assays revealed that much of the missing neuropeptide in unc-43 mutants is secreted via a regulated secretory pathway requiring UNC-31 (CAPS) and . DCV cargo levels in unc-43 mutants are similarly low in cell somas and the axon initial segment, indicating that the secretion occurs prior to axonal transport. Genetic pathway analysis suggests that abnormal neuropeptide function contributes to the sluggish basal locomotion rate of unc-43 mutants. These results reveal a novel pathway controlling the location of DCV exocytosis and describe a major new function for CaM kinase II. BOTH neurons and neuroendocrine cells rely on the controlled release of neuropeptides via dense core vesicle (DCV) exocytosis to evoke or modulate behaviors (Scheller and Axel 1984;Kupfermann 1991;T. Liu et al. 2007;Li and Kim 2008). The DCVs in neuroendocrine and PC12 cells are much more abundant and accessible to biochemical and physiological experiments than those in neurons. For example, in chromaffin and pancreatic b-cells (both neuroendocrine cells), DCVs can number in the tens of thousands per cell and can occupy 31 and 12% of the cell volume, respectively (Dean 1973;Plattner et al. 1997). Exploiting these advantages, studies in PC12 and neuroendocrine cells have revealed that DCVs arise from a regulated secretory pathway. The pathway begins in the trans Golgi, where various sorting mechanisms cause regulated secretory proteins, such as neuropeptides and their processing enzymes, to coalesce into vesicles that bud from the trans Golgi to form immature DCVs. Additional sorting of non-DCV cargos away from DCV cargos occurs as DCVs mature through this pathway (Arvan and Castle 1998;Tooze et al. 2001;Borgonovo et al. 2006).DCVs must selectively retain and protect several distinct cargos that have different physical states as they mature. These include the neuropeptide core, which is thought to be in an aggregated state, the neuropeptide-processing enzymes PC-2 convertase and carboxypeptidase E, possibly soluble cargos, and transmembrane cargos.While neurons and neuroendocrine cells share this core pathway for DCV production, neurons have evolved additional...

show abstract

Neuropeptides

Cited by 230 publications

References 116 publications

The SWI/SNF Chromatin Remodeling Complex Selectively Affects Multiple Aspects of Serotonergic Neuron Differentiation

The SWI/SNF Chromatin Remodeling Complex Selectively Affects Multiple Aspects of Serotonergic Neuron Differentiation

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

A Novel CaM Kinase II Pathway Controls the Location of Neuropeptide Release fromCaenorhabditis elegansMotor Neurons

Contact Info

Product

Resources

About