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Caenorhabditis elegans shows that sex differences in a nervous system are not simply a matter of having different numbers of neurons. The worm has a large neural network shared by males and self-fertilizing hermaphrodites, plus sex-specific cells, wiring, developmental programs, gene expression and physiology. That combination lets researchers separate how sex changes a circuit from what the circuit has in common—and offers mechanisms to test in more complex animals without proving that humans use the same circuitry.
What sexes does C. elegans have?
The laboratory nematode Caenorhabditis elegans has two sexes: males and self-fertilizing hermaphrodites. Calling the second group “female” is inaccurate for this species. Hermaphrodites produce eggs and sperm and can reproduce without a mate; males contribute sperm during mating.
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Both sexes perform many of the same basic tasks—feeding, sensing the environment, moving and avoiding danger—through a largely shared nervous system. Their differences become especially visible in reproductive behaviors. Hermaphrodites use egg-laying circuits, while males use specialized sensory, interneuron and motor pathways for locating and mating with a partner.
A shared neural core is supplemented by sex-specific neurons
A widely cited 2007 review described a “core” nervous system of exactly 294 neurons. In that accounting, hermaphrodites had eight hermaphrodite-specific neurons and males had 89 male-specific neurons. A 2018 synthesis retained the eight hermaphrodite-specific cells but counted 91 male-specific neurons. The two totals should not be silently merged: they reflect different anatomical accounts and updates to how cells were identified and classified.
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| Feature | Hermaphrodite | Male |
|---|---|---|
| Species-specific sex | Self-fertilizing hermaphrodite | Male |
| Shared neural core | 294 neurons in the 2007 account | |
| Sex-specific neurons | 8 hermaphrodite-specific neurons | 89 in the 2007 account; 91 in the 2018 synthesis |
| Representative specialized cells | HSN and VC neurons in egg-laying circuitry | CEM sensory neurons plus male-specific interneurons and motor neurons for copulation |
| Primary innate reproductive output | Egg laying and associated reproductive behaviors | Partner detection, contact, vulva location and copulation |
The numerical difference is substantial, but neuron inventory is only the first layer of sexual dimorphism. A shared neuron can still be wired differently, receive sex-specific input or operate in a different molecular state.
Three layers create sex differences in the same nervous system
1. Cell inventory: which neurons exist?
Some cells are present in only one sex. Hermaphrodite-specific HSN and VC neurons participate in egg-laying circuitry. Male-specific sensory, interneuron and motor neurons assemble pathways needed for mating and other male behaviors. This is the most visible form of dimorphism because it can be represented as a difference in cell counts.
2. Circuit wiring: how are neurons connected?
Shared neurons do not necessarily have identical synaptic partners. Reviews describe sex-specific connectivity among neurons found in both sexes, and the complete wiring maps for adult males and hermaphrodites show how sex-specific inputs enter central shared circuits. The result is a network in which reproductive signals can be routed into neurons that also participate in general-purpose behaviors.
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3. Cell state: what does each neuron express and do?
Sex can alter gene expression, neuromodulator use, membrane physiology and the behavioral effect of a neuron without changing its presence. A 2025 single-cell atlas reported differentially expressed genes in all 62 analyzed clusters of sex-shared neurons. It also connected sex-biased neuromodulatory expression with neuronal output. This distribution means there is no single “sex circuit” that explains every difference; molecular state can be shifted across much of the shared network.
How sex determination changes the nervous system during development
The X-to-autosome signal and tra-1
The worm’s sex-determination pathway begins with its X-to-autosome ratio. The transcriptional regulator tra-1 acts as the master regulator of essentially all somatic sexual characteristics. It works cell-autonomously in nearly all sexually dimorphic somatic cells, including neurons. In practical terms, a neuron can follow a male or hermaphrodite developmental program because of the sex-determination state inside that cell, not only because another organ sends it a hormonal instruction.
Programmed cell death sets different neuron complements
Developmental cell death helps produce the two nervous systems. Hermaphrodite HSN neurons survive, whereas male CEM neurons survive in the male pathway. Selective survival is therefore part of wiring the adult circuit, alongside the birth, migration and differentiation of neurons.
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NeuroPAL reveals coordinated male maturation
NeuroPAL imaging made individual male-specific neuron identities visible in living animals. The cells are generated throughout larval development, but many execute terminal differentiation in a coordinated wave during the fourth larval stage. That wave coincides with the appearance of sexual organs. The timing suggests a general developmental principle: neural maturation can be synchronized with maturation of the body’s reproductive structures, so a circuit becomes fully functional when its behavior is needed.
What the adult connectomes show
A 2019 Nature study described quantitative connectomes for both adult sexes of C. elegans: “Here we describe connectomes for both adult sexes of the nematode Caenorhabditis elegans, an important model organism for neuroscience research.” The maps provide matrices linking sensory inputs to end-organ outputs rather than a simple list of sex-specific cells.
Several findings matter for interpreting sex differences:
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- Sex-specific sensory and motor pathways are embedded in a network containing many shared neurons.
- Shared neurons can be dimorphic in structure or connectivity, even when their cell identities are present in both sexes.
- Inputs carrying sexual information enter central circuitry where they converge with pathways used for non-sexual behaviors.
- The same central network can therefore combine reproductive context with movement, sensation and internal state.
Connectomics changes the question from “Which neurons belong to males?” to “Where does sex-specific information enter, and how is it transformed before behavior?”
How the two nervous systems compare in operation
| Comparison axis | Hermaphrodite | Male |
|---|---|---|
| Neuron inventory | Eight reported hermaphrodite-specific neurons, including HSN and VC cells | 89 male-specific neurons in the 2007 account; 91 in the 2018 synthesis, including CEM cells and sex-specific motor/interneuron populations |
| Developmental timing | HSN survival and hermaphrodite reproductive circuitry are established during development | Male-specific neurons differentiate in a coordinated fourth-larval-stage wave alongside sexual-organ maturation |
| Synaptic connectivity | Egg-laying pathways use sex-specific cells and connections to shared circuits | Copulation pathways add male-specific inputs and outputs to shared central circuitry |
| Neuromodulator and gene-expression state | Shared neurons can express a hermaphrodite-biased molecular program | Shared neurons can express a male-biased program; the 2025 atlas found differential expression across all 62 analyzed shared-neuron clusters |
| Behavioral output | Egg laying and associated reproductive actions | Mate sensing, contact, vulva location and copulation |
Are sex differences only caused by extra neurons?
No. Extra neurons provide dedicated entry points and effectors, but they do not account for all dimorphism. The evidence spans three interacting levels: different cells, different synaptic connections and different molecular or physiological states in shared cells. A male and a hermaphrodite can therefore contain homologous neurons that respond differently, communicate with different partners or release different neuromodulators.
This layered organization also explains why counting neurons can underestimate behavioral differences. A small number of sex-specific cells may control access to a large shared network, while subtle state changes across dozens of shared clusters tune how that network interprets sensory information.
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What can this worm teach us about human sex differences?
C. elegans offers mechanisms and testable principles, not a direct blueprint of the human brain. Its compact nervous system makes it possible to connect genes, cell birth, synapses and behavior at whole-animal scale. Researchers can ask whether a sex-determination regulator acts directly in a neuron, whether selective cell death builds a circuit, or whether sex-biased neuromodulators alter a shared pathway.
Those are hypotheses about general biological strategies. They do not establish that human males and females have the same neuron counts, wiring diagrams or tra-1-like control logic. Humans also have far more neurons, different developmental processes and extensive interactions among genes, hormones, experience and environment. The worm is strongest as a mechanistic model: it shows how a common neural architecture can be remodeled at the levels of cells, connections and state.
Quick Recap
Key points to remember
- C. elegans has males and self-fertilizing hermaphrodites, not a simple female/male counterpart to human anatomy.
- A large shared neural core coexists with sex-specific neurons; published counts differ slightly because anatomical accounts were updated.
- Sex-specific behavior can arise from changes in cell inventory, wiring and molecular state together.
- The tra-1 pathway acts directly in many sexually dimorphic somatic cells, including neurons.
- Connectomes show sex-specific and non-sexual information converging in shared central circuitry.
- The model supports mechanistic questions about nervous-system development; it does not by itself prove a matching human circuit.
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