1. Neuroscience

A neurotransmitter atlas of C. elegans males and hermaphrodites

  1. Chen Wang  Is a corresponding author
  2. Berta Vidal
  3. Surojit Sural
  4. Curtis Loer
  5. G Robert Aguilar
  6. Daniel M Merritt
  7. Itai Antoine Toker
  8. Merly C Vogt
  9. Cyril C Cros
  10. Oliver Hobert  Is a corresponding author
  1. Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, United States
  2. Department of Biology, University of San Diego, United States
https://doi.org/10.7554/eLife.95402.3
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Cite this article
  1. Chen Wang
  2. Berta Vidal
  3. Surojit Sural
  4. Curtis Loer
  5. G Robert Aguilar
  6. Daniel M Merritt
  7. Itai Antoine Toker
  8. Merly C Vogt
  9. Cyril C Cros
  10. Oliver Hobert
(2024)
A neurotransmitter atlas of C. elegans males and hermaphrodites
eLife 13:RP95402.
https://doi.org/10.7554/eLife.95402.3
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14 figures, 2 tables and 6 additional files

Figures

Figure 1 with 1 supplement
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Background on genes examined in this paper.

(A) Neurotransmitter synthesis and transport pathways. TH = tyrosine hydroxylase; TDC = tyrosine decarboxylase; TBH = tyramine β-hydroxylase; TPH = tryptophan hydroxylase; GAD = glutamic acid …

Figure 1—figure supplement 1
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Use of aromatic amino acid decarboxylases (AAADs) in C. elegans.

(A) Biosynthesis of biogenic amines involve the use of AAADs. Modified from Figure 7 of Hobert, 2013. (B) Phylogenetic trees of amino acid decarboxylases. The only AAAD that displays reasonable …

Figure 2
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Schematics of reporter knock-in alleles.

Reporter alleles were generated by CRISPR/Cas9 genome engineering. The SL2- or T2A-based separation of the reporter from the coding sequence of the respective loci enables targeting of the reporter …

Figure 3
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Summary of neurotransmitter usage and atlases.

See Table 1, Table 2, and Supplementary files 2–4 for individual gene expression, rationale for neurotransmitter assignments, and more detailed notes. (A) ACh=acetylcholine; Glu=glutamate; …

Figure 4
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Expression of eat-4/VGLUT and unc-17/VAChT reporter alleles in the adult hermaphrodite.

Neuronal expression of eat-4(syb4257) and unc-17(syb4491) was characterized with landmark strain NeuroPAL (otIs696 and otIs669, respectively). Only selected neurons are shown for illustrating …

Figure 5
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Expression of GABA pathway genes in the adult hermaphrodite.

(A) Expression of the unc-25/GAD reporter allele ot1372 is detected in the head, ventral nerve cord, and tail neurons. The expression pattern of this new T2A-based reporter allele is similar to that …

Figure 6 with 1 supplement
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Expression of tph-1/TPH, bas-1/AAAD, and cat-1/VMAT reporter alleles in the adult hermaphrodite.

(A) Dorsoventral view of a hermaphrodite head and midbody expressing tph-1(syb6451). tph-1 expression is detected robustly in the MI neuron and dimly and variably in VC4 and VC5. Neuron identities …

Figure 6—figure supplement 1
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tph-1/TPH reporter allele expression in the hermaphrodite larvae.

Hermaphrodite heads from different larval stages (L1 to L4) and young adults expressing tph-1(syb6451). tph-1 expression in the NSML/R and ADFL/R neuron pairs and in the MI neuron was visible across …

Figure 7
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Expression of cat-2/TH, tdc-1/TDC, and tbh-1/TBH reporter alleles in the adult hermaphrodite.

Neuronal expression was characterized with landmark strain NeuroPAL (otIs669). Lateral views of young adult hermaphrodites expressing reporter alleles for (A) cat-2(syb8255), (B) tbh-1(syb7786), and …

Figure 8
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Expression of mod-5/SERT and oct-1/OCT reporter alleles in adult animals.

Neuronal expression was characterized with landmark strain NeuroPAL (otIs669) and DiD-filling. (A, C) In adult hermaphrodites, mod-5(vlc47) is expressed in sex-shared neurons NSM, ADF, RIH, AIM, …

Figure 9
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Expression of snf-3/BGT1/SLC6A12 in adult animals.

Neuronal expression was characterized with landmark strain NeuroPAL (otIs669) and DiD-filling. (A, B) In the adult hermaphrodite, neuronal expression of snf-3(syb7290) is detected in cat-1/VMAT-posit…

Figure 10
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Expression of eat-4/VGLUT and unc-17/VAChT reporter alleles in the adult male.

Neuronal expression of eat-4(syb4257) and unc-17(syb4491) was characterized with landmark strain NeuroPAL (otIs696 and otIs669, respectively). Only selected neurons are shown to illustrate updates …

Figure 11
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Expression of GABAergic reporter alleles in the adult male.

Neuronal expression of unc-25(ot1372) and unc-47(syb7566) reporter alleles was characterized with landmark strain NeuroPAL (otIs669). Only selected neurons are shown to illustrate updates from …

Figure 12
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Expression of the cat-1/VMAT, tph-1/TPH, and bas-1/AAAD reporter alleles in the adult male.

Neuronal expression was characterized with landmark strain NeuroPAL (otIs669). (A) Novel cat-1(syb6486) expression is seen in male-specific neurons PDC, PVY, PVX, R2A, and R4B. Consistent with …

Figure 13
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Expression of cat-2/TH, tdc-1/TDC, and tbh-1/TBH reporter alleles in the adult male.

Neuronal expression was characterized with landmark strain NeuroPAL (otIs669). (A) cat-2(syb8255) is expressed in male-specific neurons R4A, R7A, and R9B. This expression, as well as its expression …

Figure 14 with 1 supplement
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Expression of neurotransmitter pathway genes in non-neuronal cell types.

Multiple neurotransmitter pathway genes show expression in glial cells (A, B) and other non-neuronal cell types (C–E). Also see Figure 14—figure supplement 1 for whole-worm views that capture more …

Figure 14—figure supplement 1
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Whole-worm images showing monoaminergic pathway gene expression in different tissue types.

Monoaminergic neurotransmitter reporters show abundant expression outside of the nervous system. Lateral views of entire worms expressing the tph-1/TPH (syb6451), bas-1/AAAD (syb5923), cat-2/TH (syb8…

Tables

Table 1
Neurons that uptake monoaminergic neurotransmitters.

+: presence of reporter allele expression; -: lack of visible reporter allele expression; +/-: dim and variable expression (variability is only detected when reporter fluorescent intensity is low); …

UptakeSynthesisRelease
SerotoninNeuronmod-5tph-1cat-1
ADF+++
AIM+--
I5**--+/-
NSM+++
PVW(m)**---
RIH+-+
URX**+/---
*HSN-++
*VC4-5**-+/-+
*CEM**++-
*CP1-6+++
*PGA+-+
*R1B-++
*R3B+++
*R9B+++
TyramineNeuronoct-1tdc-1cat-1
RIM+++
BetaineNeuronsnf-3N/A***cat-1
AUA++
CAN++
NSM+/-+
RIM++
RIR+/-+
ASI+/-+
M3+/--
AIB+-
DVB+/--
SMD+/--
RIS+-
URX+/--
PDA+/--
ASG+/--
DA9+/--
VB1-11+/--
PHC+-
PVN+-
VA12+/--
RMH+/--
*PDC++
*PHD+-
*PVV+/--
Table 2
Categories of neuronal expression patterns for monoaminergic neurotransmitter pathway genes.

Criteria for monoaminergic neurotransmitter assignment and a summary for neurons with updated identities are presented here. The categories represent our best assessments based on available data; in …

Synthesis (and/or uptake)cat-1tph-1cat-2bas-1tdc-1tbh-1mod-5snf-3oct-1Direct stainingSex-specific neuronsSex-shared neurons
Tyramine+bas-1-dependent unknown monoamine?+--++----HOA
Tyramine+bas-1-dependent unknown monoamine?---++----R8A
Tyramine+dopamine+-+++----DopamineR7A
Tyramine (+uptake)+betaine (uptake)+---+--++RIM
bas-1-dependent unknown monoamine?+--+-----R2A
bas-1-dependent unknown monoamine?---+-----R3A, R6A, R6B*, PCB, SPC, DVE, DVFURB
Octopamine+---++---RIC
Octopamine----++---R8B
Dopamine+-++-----DopamineR5A, R9AADE, CEP, PDE
5-HTP (synthesis)+5-HT (alternative synthesis/uptake mechanism?)+unknown monoamine?-+---+---5-HTCEM*
5-HTP-+-------MI
PEOH?---+-+---R2B
5-HT+PEOH?-+-+-+---R7B**
5-HT+PEOH?++-+-+---5-HTR1B
5-HT+PEOH?++-+-++--5-HTR3B
5-HT+PEOH?++-+-+---R4B**
5-HT (uptake)+-----+--5-HTPGARIH
5-HT (uptake)------+--5-HTAIM
5-HT (uptake)+betaine (uptake)------++-5-HTURX*
5-HT (& uptake)++-+--+--5-HTCP1-6ADF
5-HT (alternative synthesis/uptake mechanism?)---------5-HTI5*, PVW (male only)
5-HT++-+-----5-HTHSN
5-HTP (synthesis) and 5-HT (uptake)++---++--5-HTR9B
5-HTP (synthesis) and 5-HT (alternative synthesis/uptake mechanism?)++-------5-HTVC4-5*
Unknown monoamine?+--------PVX, PVYAVL*
Unknown monoamine?-----+---HOB, R5BIL2
5-HT+betaine (uptake)++-+---+-5-HTNSM*
Betaine (uptake)+------+-PDCAUA, CAN, RIR*, ASI*
Betaine (uptake)-------+-PHD, PVV*M3*, AIB, DVB*, SMD*, RIS, PDA*, ASG*, DA9*, PHC, PVN, VA12*, VB1-11*, RMH*

Additional files

Supplementary file 1

Single-cell RNA (scRNA) data for neurotransmitters in the hermaphrodite.

Here, we show expression of previous reporters and reporter alleles used in this study, compared to scRNA data. Note that scRNA expression values for eat-4 and unc-47 can be unreliable because they were overexpressed to isolate individual neurons for scRNA analysis (Taylor et al., 2021).

https://cdn.elifesciences.org/articles/95402/elife-95402-supp1-v1.xlsx
Supplementary file 2

Updated expression patterns of neurotransmitter pathway genes in hermaphrodites.

https://cdn.elifesciences.org/articles/95402/elife-95402-supp2-v1.xlsx
Supplementary file 3

Updated expression patterns of neurotransmitter pathway genes in male-specific neurons.

https://cdn.elifesciences.org/articles/95402/elife-95402-supp3-v1.xlsx
Supplementary file 4

Summary of sexually dimorphic use of neurotransmitter pathway genes in sex-shared neurons.

https://cdn.elifesciences.org/articles/95402/elife-95402-supp4-v1.xlsx
Supplementary file 5

Summary of updates to expression patterns of classic neurotransmitter pathway genes.

https://cdn.elifesciences.org/articles/95402/elife-95402-supp5-v1.xlsx
MDAR checklist
https://cdn.elifesciences.org/articles/95402/elife-95402-mdarchecklist1-v1.docx

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