The Conserved Immunoglobulin Superfamily Member SAX-3/Robo Directs Multiple Aspects of Axon Guidance in C. elegans

Neurons form elaborate networks by guiding axons and dendrites to appropriate destinations. Neurites require information about the relative body axes during the initial projection from the cell body, and failure to receive or interpret those cues correctly can result in outgrowth errors. We identified a mutation in the Ig superfamily member syg-2 in a screen for animals with anterior/posterior (A/P) axon guidance defects. We found that syg-2 and its cognate Ig family member syg-1 appear to function in a linear genetic pathway to control the outgrowth of GABAergic axons. We determined that this pathway works in parallel to Wnt signaling. Specifically, mutations in syg-2 or syg-1 selectively affected the embryonically derived Dorsal D-type (DD) GABAergic neurons. We found no evidence that these mutations affected the Ventral D-type neurons (VD) that form later, during the first larval stage. In addition, mutations in syg-1 or syg-2 could result in the DD neurons forming multiple processes, becoming bipolar, rather than the expected pseudounipolar morphology. Given SYG-2′s essential function in synaptogenesis of the hermaphrodite-specific neurons (HSNs), we also examined DD neuron synapses in syg-2 mutants. We found syg-2 mutants had a decreased number of synapses formed, but synaptic morphology was largely normal. These results provide further evidence that the GABAergic motorneurons use multiple guidance pathways during development.

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Faculty Opinions recommendation of UNC-71, a disintegrin and metalloprotease (ADAM) protein, regulates motor axon guidance and sex myoblast migration in C. elegans.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1014098.192721 ◽

2003 ◽

Author(s):

Denise Montell

Keyword(s):

Axon Guidance ◽

Motor Axon ◽

C Elegans

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Faculty Opinions recommendation of The C. elegans L1CAM homologue LAD-2 functions as a coreceptor in MAB-20/Sema2 mediated axon guidance.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1100072.556223 ◽

2008 ◽

Author(s):

Andrew Chisholm

Keyword(s):

Axon Guidance ◽

C Elegans

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Moving around in a worm: netrin UNC-6 and circumferential axon guidance in C. elegans

Trends in Neurosciences ◽

10.1016/s0166-2236(02)02206-3 ◽

2002 ◽

Vol 25 (8) ◽

pp. 423-429 ◽

Cited By ~ 36

Author(s):

William G Wadsworth

Keyword(s):

Axon Guidance ◽

C Elegans

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Identification Of A Novel Gene Altered In The RQ1 Mutant Strain Affecting Motor Axon Migration In Caenorhabditis Elegans

10.32920/ryerson.14662620 ◽

2021 ◽

Author(s):

Haider Z. Naqvi

Keyword(s):

Caenorhabditis Elegans ◽

Axon Guidance ◽

Motor Neurons ◽

Genetic Background ◽

Germ Line ◽

Strong Indication ◽

Wild Type ◽

C Elegans ◽

Novel Gene ◽

Mutation Region

Novel genetic enhancer screens were conducted targeting mutants involved in the guidance of axons of the DA and DB classes of motor neurons in C. elegans. These mutations are expected in genes that function in parallel to the unc-g/Netrin pathway. The screen was conducted in an unc-5(e53) genetic background and enhancers of the axon guidance defects caused by the absence of UNC-5 were identified. Three mutants were previously identified in the screen called rq1, rq2 and rq3 and two additional mutants called H2-4 and M1-3, were isolated in this study. In order to identify the gene affected by the rq1 mutation, wild-type copies of genes in the mapped rq1 mutation region were injected into the mutants to rescue the phenotypic defects. This is a strong indication that the gene of interest is a novel gene called H04D03.1. Promising results indicate that the H04D03.1 protein also works in germ-line apoptosis.

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Three C. elegans Rac proteins and several alternative Rac regulators control axon guidance, cell migration and apoptotic cell phagocytosis

Development ◽

10.1242/dev.128.22.4475 ◽

2001 ◽

Vol 128 (22) ◽

pp. 4475-4488 ◽

Cited By ~ 7

Author(s):

Erik A. Lundquist ◽

Peter W. Reddien ◽

Erika Hartwieg ◽

H. Robert Horvitz ◽

Cornelia I. Bargmann

Keyword(s):

Cell Migration ◽

Axon Guidance ◽

Apoptotic Cell ◽

Regulatory Proteins ◽

Axon Pathfinding ◽

C Elegans ◽

Cell Corpse ◽

And Function ◽

Redundant Functions ◽

Caenorhabditis Elegans Genome

The Caenorhabditis elegans genome contains three rac-like genes, ced-10, mig-2, and rac-2. We report that ced-10, mig-2 and rac-2 act redundantly in axon pathfinding: inactivating one gene had little effect, but inactivating two or more genes perturbed both axon outgrowth and guidance. mig-2 and ced-10 also have redundant functions in some cell migrations. By contrast, ced-10 is uniquely required for cell-corpse phagocytosis, and mig-2 and rac-2 have only subtle roles in this process. Rac activators are also used differentially. The UNC-73 Trio Rac GTP exchange factor affected all Rac pathways in axon pathfinding and cell migration but did not affect cell-corpse phagocytosis. CED-5 DOCK180, which acts with CED-10 Rac in cell-corpse phagocytosis, acted with MIG-2 but not CED-10 in axon pathfinding. Thus, distinct regulatory proteins modulate Rac activation and function in different developmental processes.

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Molecular basis of synaptic specificity by immunoglobulin superfamily receptors in Drosophila

eLife ◽

10.7554/elife.41028 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 13

Author(s):

Shouqiang Cheng ◽

James Ashley ◽

Justyna D Kurleto ◽

Meike Lobb-Rabe ◽

Yeonhee Jenny Park ◽

...

Keyword(s):

Axon Guidance ◽

Molecular Basis ◽

Surface Proteins ◽

Synaptic Connectivity ◽

Immunoglobulin Superfamily ◽

Neuronal Connectivity ◽

Cell Surface Proteins ◽

Synaptic Specificity ◽

Immunoglobulin Superfamily Proteins ◽

Synapse Targeting

In stereotyped neuronal networks, synaptic connectivity is dictated by cell surface proteins, which assign unique identities to neurons, and physically mediate axon guidance and synapse targeting. We recently identified two groups of immunoglobulin superfamily proteins in Drosophila, Dprs and DIPs, as strong candidates for synapse targeting functions. Here, we uncover the molecular basis of specificity in Dpr–DIP mediated cellular adhesions and neuronal connectivity. First, we present five crystal structures of Dpr–DIP and DIP–DIP complexes, highlighting the evolutionary and structural origins of diversification in Dpr and DIP proteins and their interactions. We further show that structures can be used to rationally engineer receptors with novel specificities or modified affinities, which can be used to study specific circuits that require Dpr–DIP interactions to help establish connectivity. We investigate one pair, engineered Dpr10 and DIP-α, for function in the neuromuscular circuit in flies, and reveal roles for homophilic and heterophilic binding in wiring.

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Regulation of axon repulsion by MAX-1 SUMOylation and AP-3

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1804373115 ◽

2018 ◽

Vol 115 (35) ◽

pp. E8236-E8245

Author(s):

Shih-Yu Chen ◽

Chun-Ta Ho ◽

Wei-Wen Liu ◽

Mark Lucanic ◽

Hsiu-Ming Shih ◽

...

Keyword(s):

Axon Guidance ◽

Neural Development ◽

Biochemical Analysis ◽

Genetic Interaction ◽

Motor Axons ◽

Surface Receptors ◽

C Elegans ◽

Guidance Receptors ◽

Axon Repulsion

During neural development, growing axons express specific surface receptors in response to various environmental guidance cues. These axon guidance receptors are regulated through intracellular trafficking and degradation to enable navigating axons to reach their targets. In Caenorhabditis elegans, the UNC-5 receptor is necessary for dorsal migration of developing motor axons. We previously found that MAX-1 is required for UNC-5–mediated axon repulsion, but its mechanism of action remained unclear. Here, we demonstrate that UNC-5–mediated axon repulsion in C. elegans motor axons requires both max-1 SUMOylation and the AP-3 complex β subunit gene, apb-3. Genetic interaction studies show that max-1 is SUMOylated by gei-17/PIAS1 and acts upstream of apb-3. Biochemical analysis suggests that constitutive interaction of MAX-1 and UNC-5 receptor is weakened by MAX-1 SUMOylation and by the presence of APB-3, a competitive interactor with UNC-5. Overexpression of APB-3 reroutes the trafficking of UNC-5 receptor into the lysosome for protein degradation. In vivo fluorescence recovery after photobleaching experiments shows that MAX-1 SUMOylation and APB-3 are required for proper trafficking of UNC-5 receptor in the axon. Our results demonstrate that SUMOylation of MAX-1 plays an important role in regulating AP-3–mediated trafficking and degradation of UNC-5 receptors during axon guidance.

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