Syndecan functions to regulate Wnt-dependent axon guidance in C. elegans

AbstractCell adhesion molecules are key to axon guidance during development, for example specific cues can instruct axons to terminate in a specific area, or to continue growth. Syndecans are conserved cell-surface receptors that function in multiple developmental contexts. Caenorhabditis elegans with mutations in the single syndecan gene, sdn-1, exhibited errors in anterior-posterior guidance, with axons that stopped short of, or grew past their stereotypical termination point. Syndecan function was cell non-autonomous for GABAergic axon outgrowth during early development, but was likely cell autonomous to inhibit growth later in development. sdn-1 appeared to regulate the inhibitory activity of the egl-20/Wnt ligand. Removing egl-20 from sdn-1 mutants resulted in fewer animals with prematurely terminating axons. The proteoglycan modifying enzymes hse-5 and hst-2, but not hst-6, had similar effects, suggesting specific heparan sulfate modifications regulated EGL-20 axon-terminating activity. sdn-1 functioned with lin-17/Frizzled, bar-1/β-catenin and the egl-5 Hox-like transcription factor in EGL-20-depedent axon outgrowth. bar-1 was required for egl-5 expression in the most posterior GABAergic neurons. sdn-1 mutations did not eliminate egl-5 expression, but over-expression of egl-5 rescued sdn-1 phenotypes. Our results suggest syndecan is a component of Wnt-signaling events that are necessary for axons to recognize appropriate termination points.

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Faculty Opinions recommendation of Wnt signals and frizzled activity orient anterior-posterior axon outgrowth in C. elegans.

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

10.3410/f.1022787.367930 ◽

2006 ◽

Author(s):

Catherine Krull

Keyword(s):

Axon Outgrowth ◽

C Elegans ◽

Anterior Posterior

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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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Faculty Opinions recommendation of Wnt signals and frizzled activity orient anterior-posterior axon outgrowth in C. elegans.

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

10.3410/f.1022787.369704 ◽

2006 ◽

Author(s):

Shai Shaham

Keyword(s):

Axon Outgrowth ◽

C Elegans ◽

Anterior Posterior

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Semaphorin 1a and semaphorin 1b are required for correct epidermal cell positioning and adhesion during morphogenesis in C. elegans

Development ◽

10.1242/dev.129.9.2065 ◽

2002 ◽

Vol 129 (9) ◽

pp. 2065-2078

Author(s):

Val E. Ginzburg ◽

Peter J. Roy ◽

Joseph G. Culotti

Keyword(s):

Axon Guidance ◽

Transmembrane Proteins ◽

Precursor Cell ◽

Deletion Mutants ◽

Normal Position ◽

C Elegans ◽

Seam Cell ◽

Ray Cells ◽

Cell Positioning ◽

Anterior Posterior

The semaphorin family comprises secreted and transmembrane proteins involved in axon guidance and cell migration. We have isolated and characterized deletion mutants of C. elegans semaphorin 1a (Ce-sema-1a or smp-1) and semaphorin 1b (Ce-sema-1b or smp-2) genes. Both mutants exhibit defects in epidermal functions. For example, the R1.a-derived ray precursor cells frequently fail to change anterior/posterior positions completely relative to their sister tail lateral epidermal precursor cell R1.p, causing ray 1 to be formed anterior to its normal position next to ray 2. The ray cells, which normally separate from the lateral tail seam cell (SET) at the end of L4 stage, remains connected to the SET cell even in adult mutant males. The ray 1 defects are partially penetrant in each single Ce-sema-1 mutant at 20°C, but are greatly enhanced in Ce-sema-1 double mutants, suggesting that Ce-Sema-1a and Ce-Sema-1b function in parallel to regulate ray 1 position. Both mutants also have defects in other aspects of epidermal functions, including head and tail epidermal morphogenesis and touch cell axon migration, whereas, smp-1 mutants alone have defects in defecation and brood size. A feature of smp-1 mutants that is shared with mutants of mab-20 (which encodes Sema-2a) is the abnormal perdurance of contacts between epidermal cells.

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The Immunoglobulin Superfamily Members syg-2 and syg-1 Regulate Neurite Development in C. elegans

Journal of Developmental Biology ◽

10.3390/jdb10010003 ◽

2022 ◽

Vol 10 (1) ◽

pp. 3

Author(s):

Dana K. Tucker ◽

Chloe S. Adams ◽

Gauri Prasad ◽

Brian D. Ackley

Keyword(s):

Axon Guidance ◽

Immunoglobulin Superfamily ◽

Genetic Pathway ◽

C Elegans ◽

Multiple Processes ◽

Ig Superfamily ◽

Essential Function ◽

Neurite Development ◽

To Receive ◽

Anterior Posterior

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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