Xiajing Tong, PhDAssociate Professor

Genetic Contributions

1. Sexually Dimorphic Cholinergic Transmission at C. elegans NMJs Mediates Sex-Specific Locomotion Behaviors In C. elegans, there are two sexes: somatic female hermaphrodites and males. These two sexes exhibit distinct motor behaviors, with males showing faster locomotion velocities and more pronounced body wave curvatures compared to hermaphrodites. Our study reveals sexually dimorphic cholinergic synaptic transmission at the neuromuscular junctions (NMJs), with males exhibiting increased synaptic release frequencies. Scanning electron microscopy further demonstrated that males have significantly more synaptic vesicles (SVs) at their cholinergic synapses compared to hermaphrodites that is mediated by CaMKII. Thus, beyond demonstrating UNC-43/CaMKII as an essential mediator of sex-specific synaptic transmission, our study provides molecular and cellular insights into how sex-shared neurons can generate sexually dimorphic locomotion behaviors. ( J Cell Biol., 2023).

2. Presynaptic CaMKII Triggers Anterograde Signaling to Recruit GABAARs A key mechanism for modulating inhibitory synaptic transmission and plasticity is the regulation of postsynaptic GABA receptor (GABAAR) abundance. Recent studies, including our own, have shown that GABAARs are stabilized by distinct scaffolds at C. elegans NMJs, including the synaptic adhesion molecule NLG-1/Neuroligin and the FERM domain-containing protein FRM-3 (Elife, 2015; PLOS Genetics, 2023). In this study, we identify UNC-43/CaMKII, the C. elegans ortholog of CaMKII, as a crucial factor in initiating anterograde signals (MADD-4B/Punctin and NRX-1α) that recruit postsynaptic GABAARs, modulating inhibitory synaptic transmission. Our findings provide new insights into how presynaptic neurons transsynaptically recruit postsynaptic receptors during synaptogenesis and activity-dependent plasticity (Nature Communications, 2023).

Environmental Contributions

3. Male Pheromones Modulate Cholinergic Transmission at Hermaphrodite NMJs We show that male-specific pheromones (ascarosides) increase cholinergic synaptic transmission at the NMJs in C. elegans in a sex-specific manner—specifically in hermaphrodites. This pheromone-mediated modulation of cholinergic transmission is developmental stage-dependent. Upon detection, AWB neurons utilize cGMP signaling to relay the information to NMJs. Furthermore, we find that activation of AWB neurons during the early developmental stages (L3-L4) is both necessary and sufficient to modulate cholinergic transmission at NMJs. These findings provide new insights into how animals sense and adapt to their social environments, highlighting the role of pheromones in regulating development and behavior (Elife, 2021; Journal of Cell Science, 2022).

4. Pheromone Exposure During Early Development Promotes Neurodegeneration in Adults Neurodegenerative diseases have significant environmental components, including exposure to chemical cues. In C. elegans, we found that exposure to specific pheromones (ascr#3 and ascr#10) during the early developmental stage (L1) remodels neurodevelopment and accelerates α-synuclein-induced neurodegeneration in adult hermaphrodites. We identified two pairs of chemosensory neurons, ASK and ASI, that mediate the perception of ascr#3 and ascr#10, respectively. Activation of both ASI and ASK neurons during the L1 stage is sufficient to remodel neurodevelopment through AIA interneurons, which trigger insulin-like signaling and inhibit autophagy in adult neurons in a non-cell-autonomous manner. Our work uncovers a mechanism by which pheromone perception during early development influences neurodevelopment and alters autophagy and proteotoxicity-induced neurodegeneration in adulthood. These findings offer important insights into how environmental factors influence the progression of neurodegenerative diseases (Cell Reports, 2023).