Precisely localized guidance signals instruct dendrite branching and morphogenesis
Abstract/Contents
- Abstract
- The establishment of a complex, cell type-specific dendritic arbor is crucial for many neurons to receive the appropriate inputs from their receptive fields and to properly function within a neural circuit. However, the immense complexity of dendrite morphology has made it far more challenging to study than the pathfinding of a single axon. In the model nematode Caenorhabditis elegans, the sensory neuron PVD establishes stereotypical, highly-branched dendrite morphology. Using genetic approaches, we identified a novel ligand-receptor complex of membrane adhesion molecules that is both necessary and sufficient to instruct spatially restricted growth and branching of PVD dendrites. The ligand complex SAX-7/L1CAM and MNR-1 function at defined locations in the surrounding hypodermal tissue, while DMA-1 and HPO-30/Claudin act as cognate co-receptors in PVD. Mutations in this complex lead to dramatic defects in the formation, stabilization, and organization of the dendritic arbor. Ectopic expression of SAX-7 and MNR-1 generates a predictable, unnaturally patterned dendritic tree in a DMA-1 and HPO-30 dependent manner. Both in vivo and in vitro experiments indicate that these molecules function as a ligand-receptor complex to instruct dendrite morphogenesis. Similar to developing axons, growing dendrites also encounter intermediate targets marked by guidance signals but must switch their response upon arrival so that they can move away and complete the next stage of development. During the development of wild-type PVD neurons, dendrites bypass a zone of high level SAX-7 without responding to the signal. We found that in mutants lacking KPC-1, a C. elegans Furin homolog, dendrites fail to escape from this intermediate target but are trapped in the area. Further analysis revealed that KPC-1 down-regulates the level of the branching receptor DMA-1 on dendrites by targeting it to late endosomes. In a kpc-1 mutant, the level of DMA-1 is abnormally high on dendrites, resulting in trapping of dendrites at locations where a high level of SAX-7 is present. Thus, precise regulation of guidance receptors creates flexibility of responses to guidance signals and is critical for neuronal morphogenesis. In summary, we identified a pair of skin-derived, precisely localized guidance molecules that instruct dendrite morphogenesis and their cognate neuronal receptors, as well as an intracellular mechanism that regulates membrane targeting of the dendritic receptor to ensure that signalling happens at the right place and right time.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2015 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Dong, Xintong |
|---|---|
| Associated with | Stanford University, Department of Biology. |
| Primary advisor | Shen, Kang, 1972- |
| Thesis advisor | Shen, Kang, 1972- |
| Thesis advisor | Clandinin, Thomas R. (Thomas Robert), 1970- |
| Thesis advisor | Luo, Liqun, 1966- |
| Advisor | Clandinin, Thomas R. (Thomas Robert), 1970- |
| Advisor | Luo, Liqun, 1966- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Xintong Dong. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2015. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2015 by Xintong Dong
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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