Troemel E (2018) BMC Biol "Host-parasite interactions: an interview with Emily Troemel."

Troemel E

[BMC Biol, 2018]

Emily Troemel is a Professor at the University of California San Diego, where her lab uses Caenorhabditis elegans to study host-pathogen interactions and the shaping of the immune response. In this interview, Emily shared her thoughts on peer review and its role in training future scientists, and the possibility of a new form of immunity in epithelia.

Xu Y et al. (2016) Dev Biol "Transition between synaptic branch formation and synaptogenesis is regulated by the lin-4 microRNA."

Quinn CC, Xu Y

[Dev Biol, 2016]

Axonal branch formation and synaptogenesis are sequential events that are required for the establishment of neuronal connectivity. However, little is known about how the transition between these two events is regulated. Here, we report that the lin-4 microRNA can regulate the transition between branch formation and synaptogenesis in the PLM axon of C. elegans. The PLM axon grows a collateral branch during the early L1 stage and undergoes synaptogenesis during the late L1 stage. Loss of the lin-4 microRNA disrupts synaptogenesis during the late L1 stage, suggesting that lin-4 promotes synaptogenesis. Conversely, the target of lin-4, the LIN-14 transcription factor, promotes PLM branch formation and inhibits synaptogenesis during the early L1 stage. Moreover, we present genetic evidence suggesting that synaptic vesicle transport is required for PLM branch formation and that the role of LIN-14 is to promote transport of synaptic vesicles to the region of future branch growth. These observations provide a novel mechanism whereby lin-4 promotes the transition from branch formation to synaptogenesis by repressing the branch-promoting and synaptogenesis-inhibiting activities of LIN-14.

Vasudevan A et al. (2024) Genetics "Preferential transport of synaptic vesicles across neuronal branches is regulated by the levels of the anterograde motor UNC-104/KIF1A in vivo."

Kumari S, Ratnakaran N, Koushika SP, Vasudevan A, Murthy K, Hall DH

[Genetics, 2024]

Asymmetric transport of cargo across axonal branches is a field of active research. Mechanisms contributing to preferential cargo transport along specific branches in vivo in wild type neurons are poorly understood. We find that anterograde synaptic vesicles preferentially enter the synaptic branch or pause at the branch point in C. elegans PLM neurons. The synaptic vesicle anterograde kinesin motor UNC-104/KIF1A regulates this vesicle behaviour at the branch point. Reduced levels of functional UNC-104 cause vesicles to predominantly pause at the branch point and lose their preference for turning into the synaptic branch. SAM-4/Myrlysin, which aids in recruitment/activation of UNC-104 on synaptic vesicles, regulates vesicle behaviour at the branch point similar to UNC-104. Increasing the levels of UNC-104 increases the preference of vesicles to go straight towards the asynaptic end. This suggests that the neuron optimises UNC-104 levels on the cargo surface to maximise the fraction of vesicles entering the branch and minimise the fraction going to the asynaptic end.

Vasudevan A et al. (2024) MicroPubl Biol "Physical presence of chemical synapses is necessary for turning behavior of anterograde synaptic vesicles at the branch point of PLM neurons in C. elegans."

Vasudevan A, Koushika SP

[MicroPubl Biol, 2024]

Neurons exhibit complex branched axonal morphologies in both vertebrate and invertebrate systems, and show heterogeneity in the distribution of synaptic cargo across multiple synapses. It is possible that differences in transport across multiple branches contribute to the heterogeneity in cargo distribution across multiple synapses. However, the regulation of transport at axonal branch points is not well understood. We demonstrate that branch-specific transport of synaptic vesicles is dependent on the existence of a connection between the branch and synapses. The loss of this connection causes an immediate decrease in branch-specific transport of synaptic vesicles in the PLM neuron of <i>C. elegans</i> .

Walthall WW et al. (1986) Worm Breeder's Gazette "more on the developmental interactions between AVM and the BDU neurons."

Masuoka C, Chalfie M, Walthall WW

[Worm Breeder's Gazette, 1986]

We previously reported that ablation of the BDU cells at hatching disrupts the ability of the postembryonic touch cell AVM to mediate a head touch response (CSH meeting, 1985). This dependence of AVM on the BDU cells is restricted to early postembryonic development, as removal o at 24 hours or more after hatching no longer affects the touch sensitivity mediated by AVM. We have examined in the electron microscope AVM neurons that have grown in the absence of the BDU cells and found a range of changes in the morphology of the synaptic branch. Five animals were examined: one had a normal synaptic branch directed toward the nerve ring; a second had a small, anteriorly displaced branch that appeared to enter one of the circumferential commissures In the other three no sign of a synaptic branch was seen We interpret these results to mean that the process giving rise to the synaptic branch of the postembryonic AVM is dependent upon the presence of the BDU neurons BDU may affect AVM development in two ways. First, the BDU cell may induce the formation of the synaptic branch. Alternatively, BDU may provide a path into the nerve ring and the synapses formed between these cells serve both to stabilize the branch and to guide it through an essentially mature nerve ring In the absence of the stabilizing influence the branch must find an alternative to survive Because branches were present in two of the five animals we examined and because based on adult reconstructions White, et al , 1986) the AVM process appears to branch before contacting the BDU cell, we favor the second hypothesis

Vasudevan, A. et al. (2019) International Worm Meeting "Regulation of synaptic vesicle transport at neuronal branch points in vivo."

Koushika, S. P., Ratnakaran, N., Murthy, K., Ahlawat, S., Vasudevan, A., Venkatesh, K.

[International Worm Meeting, 2019]

Neurons exhibit complex branched axonal morphologies across vertebrate and invertebrate systems. It remains unknown whether the distribution of axonal cargo across multiple branches is a random or regulated phenomenon. We addressed this question by using the C. elegans PLM Touch Receptor Neuron as our model system. Using live imaging, we found that synaptic vesicles preferentially turn into the PLM branch or pause at the branch point, as opposed to going straight along the main neuronal process. Our observations suggest that this behaviour could be regulated by (a) the underlying microtubule geometry at the branch point and/or (b) the anterograde motor UNC-104, which transports synaptic vesicles along the neuronal process. We investigated the microtubule layout at the branch point by immunostaining for tubulin and its different post-translational modifications. Preliminary data suggested that the branch shows a similar distribution of acetylated microtubules to that in the main process. Lower and higher levels of UNC-104 (in the neuronal process and on the vesicle surface) were seen to regulate distinct vesicle behaviors at the branch point. Interestingly, the turning behavior of anterograde vesicles was reduced when the levels of the retrograde motor subunit, DHC-1, were lowered, suggesting that a balance between the levels of the anterograde and retrograde motor may be important for regulating the behaviour of these vesicles at the branch point. This is a novel study that examines cargo transport at axonal branch points in vivo and hints at underlying motor-related mechanisms that govern their behaviour.

Morris JZ et al. (1995) International C. elegans Meeting "MAPPING AND CLONING daf-23"

Ruvkun GB, Morris JZ

[International C. elegans Meeting, 1995]

The dauer formation pathway requires the animal to assimilate environmental inputs (food, pher- omone, and temperature) and regulate its dev- elopment (as a dauer or an L3 larvae) accordingly. We are cloning the gene daf-23, a maternal effect dauer constitutive gene which acts in the daf-23/ daf-2/daf-16/daf-18 branch of the dauer genetic epistasis pathway. This branch has dramatic effects on senescence as well as on dauer form- ation. Unlike the other branches of the dauer pathway, this branch has no known pleiotropies, suggesting that it acts downstream of the sensory neurons, perhaps in secretory neurons or in down- stream tissues.

Hekimi S et al. (1993) J Neurosci "Axonal guidance defects in a Caenorhabditis elegans mutant reveal cell-extrinsic determinants of neuronal morphology."

Kershaw D, Hekimi S

[J Neurosci, 1993]

Mutations in the gene unc-53 of Caenorhabditis elegans result in behavioral and anatomical abnormalities. Immunocytochemistry and electron microscopy revealed neuroanatomical defects in all main longitudinal nervous tracts. Whole tracts were found to be misguided in specific ways suggesting that unc-53 affects pioneering axons. The four lateral microtubule cells (LMs), which are probably pioneering neurons, were examined in greatest detail. In the mutants, the processes of the LMs leave their normal position on the body wall and terminate prematurely. Examination of five unc-53 alleles for penetrance and expressivity of these defects revealed a spatial restriction in the requirement for unc-53. The morphology and positioning of the branch of the posterior lateral microtubule cells (PLMs) were also examined. In wild-type animals, the PLM branches lack the ultrastructural specializations of the main process, which include large microtubules, apposition to the cuticle, and a polarized extracellular matrix (the mantle). Two differences were noted in unc-53 mutants. First, a majority of PLMs branch at random and display an abnormally enlarged branching point and branch cross section. The unusual branch morphologies correlate with branch position, rather than PLM length. Second, the ectopic branches display the specific ultrastructural features characteristic of the main process. Furthermore, after entering the ventral nerve cord, the abnormal branches constantly change position relative to the other processes and the hypodermis, retaining their specialized microtubules throughout, but displaying a mantle only when in direct contact with hypodermis. Taken together, these observations suggest that the differentiated features of the PLMs, including process length, branch position, intracellular branch morphology, and surrounding extracellular matrix, are locally specified by cell-extrinsic cues, some of which require unc-53.

Jin H et al. (2020) Front Neuroanat "Neurite Branching Regulated by Neuronal Cell Surface Molecules in Caenorhabditis elegans."

Jin H, Kim B

[Front Neuroanat, 2020]

The high synaptic density in the nervous system results from the ability of neurites to branch. Neuronal cell surface molecules play central roles during neurite branch formation. The underlying mechanisms of surface molecule activity have often been elucidated using invertebrates with simple nervous systems. Here, we review recent advances in understanding the molecular mechanisms of neurite branching in the nematode <i>Caenorhabditis elegans</i>. We discuss how cell surface receptor complexes link to and modulate actin dynamics to regulate dendritic and axonal branch formation. The mechanisms of neurite branching are often coupled with other neural circuit developmental processes, such as synapse formation and axon guidance, <i>via</i> the same cell-cell surface molecular interactions. We also cover ectopic and sex-specific neurite branching in <i>C. elegans</i> in an attempt to illustrate the importance of these studies in contributing to our understanding of conserved cell surface molecule regulation of neurite branch formation.

Chen, Chun-Hao et al. (2013) International Worm Meeting "Microtubules-Based Inhibition of RhoA and MAPK Signaling Promotes Synapse Maturation and Axon Branch Maintenance in C. elegans."

Chen, Chun-Hao, Pan, Chun-Liang, Lee, Yu-Hsien

[International Worm Meeting, 2013]

Connectivity of the neuronal circuit is refined by the dynamic regulation of synapse formation and elimination. While mechanisms that promote synapse formation had been studied in detail, those that maintain established synapses are still poorly understood. We identified two tubulin genes, mec-12/a-tubulin and mec-7/b-tubulin, as essential for synapse and axon branch maintenance. In the mec-12 and the mec-7 mutants, the PLM synapses formed normally but were progressively lost, with concomitant retraction of the PLM axon branch. The synapse and axon branch defects of the tubulin mutants were suppressed by mutations in rhgf-1, a RhoGEF with potential microtubule association. Genetic analysis suggested that the GEF activity of rhgf-1 triggered synaptic and axon branch defects and that the PDZ and the C1 domains may inhibit this GEF activity. We further demonstrated that RHGF-1 acted through the Rho (rho-1), the Rac (ced-10 and mig-2) and the Rho kinase let-502/ROCK, but independently of the canonical ROCK target MLC-4/myosin regulatory light chain. Instead, it activated a conserved p38/MAPK pathway, consisting of dlk-1/MAPKKK, mkk-4/MAPKK, and pmk-3/MAPK. DLK-1 was required and sufficient to promote PLM branch retraction cell-autonomously through sequential phosphorylation of MKK-4 and PMK-3. These MAPK components were expressed both at the synapse and in the neuronal soma. Interestingly, we found that blocking the dynein-based retrograde transport significantly reduced axon branch defects of the mec-7 mutants. We propose a model in which microtubules disassembly activates MAPK signaling through ROCK, and this MAPK activity is part of the retrograde signals that induce subsequent axon retraction upon microtubule loss. Our work had identified molecular mechanisms by which microtubules promote synaptic stability and axon branch maintenance in the neurons. This work is supported by the National Science Council, Taiwan (NSC99-2320-B-002-080 and NSC100-2320-B-002-095-MY3) and National Taiwan University (NTU-CDP-102R7810).