Limits...
Neuroendocrine modulation sustains the C. elegans forward motor state

View Article: PubMed Central - PubMed

ABSTRACT

Neuromodulators shape neural circuit dynamics. Combining electron microscopy, genetics, transcriptome profiling, calcium imaging, and optogenetics, we discovered a peptidergic neuron that modulates C. elegans motor circuit dynamics. The Six/SO-family homeobox transcription factor UNC-39 governs lineage-specific neurogenesis to give rise to a neuron RID. RID bears the anatomic hallmarks of a specialized endocrine neuron: it harbors near-exclusive dense core vesicles that cluster periodically along the axon, and expresses multiple neuropeptides, including the FMRF-amide-related FLP-14. RID activity increases during forward movement. Ablating RID reduces the sustainability of forward movement, a phenotype partially recapitulated by removing FLP-14. Optogenetic depolarization of RID prolongs forward movement, an effect reduced in the absence of FLP-14. Together, these results establish the role of a neuroendocrine cell RID in sustaining a specific behavioral state in C. elegans.

Doi:: http://dx.doi.org/10.7554/eLife.19887.001

No MeSH data available.


Related in: MedlinePlus

The expression pattern of UNC-39::GFP and phenotypes of unc-39 mutants.(A) During embryogenesis, unc-39::GFP is expressed in both RID (arrowhead) and the RID sister cell (arrow) (t1), before the latter dies as a result of apoptosis (t2). (B) Known RID cell fate markers, such as kal-1 (top panel), ser-2 (middle panel), and mod-1 (bottom panel) are present in wild type animals (arrow), but not unc-39 mutants hp701 and e257. (C) During early embryogenesis, the RID lineage-specific apoptosis activator UNC-3 is expressed in RID and the RID sister cell, but not in unc-39 mutants. (D) The absence of RID in unc-39 mutants is not due to ectopic apoptosis. Bottom Left, A schematic of the RID cell lineage: the ABalappaa neuroblast undergoes two consecutive rounds of mitosis to give rise to RID. Both the sisters of the RID precursor and RID undergo apoptosis. Top Panel, Apoptotic mutants ced-3 and ced-4 possess two RID neurons resulting from failure to activate apoptosis in the RID sister (arrowheads). However, a majority of unc-39; ced-3 and unc-39; ced-4 mutants still do not possess RID. Bottom Right, Quantification of genetic interaction from top panel. N = 10 animals/genotype. For B, C, and D, the putative position of RID and/or RID sister cell in unc-39 mutants is designated by a circle.DOI:http://dx.doi.org/10.7554/eLife.19887.005
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5120884&req=5

fig2s1: The expression pattern of UNC-39::GFP and phenotypes of unc-39 mutants.(A) During embryogenesis, unc-39::GFP is expressed in both RID (arrowhead) and the RID sister cell (arrow) (t1), before the latter dies as a result of apoptosis (t2). (B) Known RID cell fate markers, such as kal-1 (top panel), ser-2 (middle panel), and mod-1 (bottom panel) are present in wild type animals (arrow), but not unc-39 mutants hp701 and e257. (C) During early embryogenesis, the RID lineage-specific apoptosis activator UNC-3 is expressed in RID and the RID sister cell, but not in unc-39 mutants. (D) The absence of RID in unc-39 mutants is not due to ectopic apoptosis. Bottom Left, A schematic of the RID cell lineage: the ABalappaa neuroblast undergoes two consecutive rounds of mitosis to give rise to RID. Both the sisters of the RID precursor and RID undergo apoptosis. Top Panel, Apoptotic mutants ced-3 and ced-4 possess two RID neurons resulting from failure to activate apoptosis in the RID sister (arrowheads). However, a majority of unc-39; ced-3 and unc-39; ced-4 mutants still do not possess RID. Bottom Right, Quantification of genetic interaction from top panel. N = 10 animals/genotype. For B, C, and D, the putative position of RID and/or RID sister cell in unc-39 mutants is designated by a circle.DOI:http://dx.doi.org/10.7554/eLife.19887.005

Mentions: UNC-39 is a homeobox transcription factor of the Six/SO family. Six/SO is necessary for the development of the fruit fly eye (Cheyette et al., 1994), the insect endocrine gland corpora cardiac (De Velasco et al., 2004), and the vertebrate forebrains (Lagutin et al., 2003). C. elegans unc-39 mutants exhibit variable defects in post-embryonic mesodermal differentiation, soma or neurite migration, and expression of terminal fate markers in several neurons (Manser and Wood, 1990; Yanowitz et al., 2004). As previously reported (Yanowitz et al., 2004), our unc-39 reporters (Supplemental Methods) were expressed by muscles and multiple neurons during embryonic development and into the adulthood (Figure 2C). Notably, we observed robust expression of unc-39 reporters in the embryonic RID precursor (Figure 2—figure supplement 1A), embryonic RID (Figure 2C, top panel), and newly hatched L1 larvae (Figure 2C, middle panel). Post-embryonically, unc-39 expression was selectively decreased in some neurons, including RID (Figure 2C, lower panels).


Neuroendocrine modulation sustains the C. elegans forward motor state
The expression pattern of UNC-39::GFP and phenotypes of unc-39 mutants.(A) During embryogenesis, unc-39::GFP is expressed in both RID (arrowhead) and the RID sister cell (arrow) (t1), before the latter dies as a result of apoptosis (t2). (B) Known RID cell fate markers, such as kal-1 (top panel), ser-2 (middle panel), and mod-1 (bottom panel) are present in wild type animals (arrow), but not unc-39 mutants hp701 and e257. (C) During early embryogenesis, the RID lineage-specific apoptosis activator UNC-3 is expressed in RID and the RID sister cell, but not in unc-39 mutants. (D) The absence of RID in unc-39 mutants is not due to ectopic apoptosis. Bottom Left, A schematic of the RID cell lineage: the ABalappaa neuroblast undergoes two consecutive rounds of mitosis to give rise to RID. Both the sisters of the RID precursor and RID undergo apoptosis. Top Panel, Apoptotic mutants ced-3 and ced-4 possess two RID neurons resulting from failure to activate apoptosis in the RID sister (arrowheads). However, a majority of unc-39; ced-3 and unc-39; ced-4 mutants still do not possess RID. Bottom Right, Quantification of genetic interaction from top panel. N = 10 animals/genotype. For B, C, and D, the putative position of RID and/or RID sister cell in unc-39 mutants is designated by a circle.DOI:http://dx.doi.org/10.7554/eLife.19887.005
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120884&req=5

fig2s1: The expression pattern of UNC-39::GFP and phenotypes of unc-39 mutants.(A) During embryogenesis, unc-39::GFP is expressed in both RID (arrowhead) and the RID sister cell (arrow) (t1), before the latter dies as a result of apoptosis (t2). (B) Known RID cell fate markers, such as kal-1 (top panel), ser-2 (middle panel), and mod-1 (bottom panel) are present in wild type animals (arrow), but not unc-39 mutants hp701 and e257. (C) During early embryogenesis, the RID lineage-specific apoptosis activator UNC-3 is expressed in RID and the RID sister cell, but not in unc-39 mutants. (D) The absence of RID in unc-39 mutants is not due to ectopic apoptosis. Bottom Left, A schematic of the RID cell lineage: the ABalappaa neuroblast undergoes two consecutive rounds of mitosis to give rise to RID. Both the sisters of the RID precursor and RID undergo apoptosis. Top Panel, Apoptotic mutants ced-3 and ced-4 possess two RID neurons resulting from failure to activate apoptosis in the RID sister (arrowheads). However, a majority of unc-39; ced-3 and unc-39; ced-4 mutants still do not possess RID. Bottom Right, Quantification of genetic interaction from top panel. N = 10 animals/genotype. For B, C, and D, the putative position of RID and/or RID sister cell in unc-39 mutants is designated by a circle.DOI:http://dx.doi.org/10.7554/eLife.19887.005
Mentions: UNC-39 is a homeobox transcription factor of the Six/SO family. Six/SO is necessary for the development of the fruit fly eye (Cheyette et al., 1994), the insect endocrine gland corpora cardiac (De Velasco et al., 2004), and the vertebrate forebrains (Lagutin et al., 2003). C. elegans unc-39 mutants exhibit variable defects in post-embryonic mesodermal differentiation, soma or neurite migration, and expression of terminal fate markers in several neurons (Manser and Wood, 1990; Yanowitz et al., 2004). As previously reported (Yanowitz et al., 2004), our unc-39 reporters (Supplemental Methods) were expressed by muscles and multiple neurons during embryonic development and into the adulthood (Figure 2C). Notably, we observed robust expression of unc-39 reporters in the embryonic RID precursor (Figure 2—figure supplement 1A), embryonic RID (Figure 2C, top panel), and newly hatched L1 larvae (Figure 2C, middle panel). Post-embryonically, unc-39 expression was selectively decreased in some neurons, including RID (Figure 2C, lower panels).

View Article: PubMed Central - PubMed

ABSTRACT

Neuromodulators shape neural circuit dynamics. Combining electron microscopy, genetics, transcriptome profiling, calcium imaging, and optogenetics, we discovered a peptidergic neuron that modulates C. elegans motor circuit dynamics. The Six/SO-family homeobox transcription factor UNC-39 governs lineage-specific neurogenesis to give rise to a neuron RID. RID bears the anatomic hallmarks of a specialized endocrine neuron: it harbors near-exclusive dense core vesicles that cluster periodically along the axon, and expresses multiple neuropeptides, including the FMRF-amide-related FLP-14. RID activity increases during forward movement. Ablating RID reduces the sustainability of forward movement, a phenotype partially recapitulated by removing FLP-14. Optogenetic depolarization of RID prolongs forward movement, an effect reduced in the absence of FLP-14. Together, these results establish the role of a neuroendocrine cell RID in sustaining a specific behavioral state in C. elegans.

Doi:: http://dx.doi.org/10.7554/eLife.19887.001

No MeSH data available.


Related in: MedlinePlus