regeneration in nature

Home » Fish » Syntenin-a promotes spinal cord regeneration in zebrafish

Syntenin-a promotes spinal cord regeneration in zebrafish

As discussed before in this blog mammalian central nervous system fails to regenerate because of a combination of extrinsic and intrinsic inhibitory factors. So far, and despite different approaches based on attempts to neutralize those inhibitory cues, recreate permissive environments or transplant stem cells, there is no promising therapy for spinal cord injury patients yet. Therefore it is important to understand how other vertebrates do to regenerate their central nervous system. Among these, zebrafish are able to regenerate their spinal cord after injury. A recent study from the laboratory of Melitta Schachner reports on the role of syntenin-a in promoting spinal cord regeneration in zebrafish (http://www.ncbi.nlm.nih.gov/pubmed/23607754).

Syntenins are scaffolding proteins identified as syndecan-binding proteins and that contain multiple PDZ domains to bind the cytoplasmic domain of a variety of transmembrane proteins. Syntenins have been involved in cytoskeleton signalling, protein trafficking, cell adhesion, migration, activation of transcription factors and cytoskeletal reorganization in some cancer lines. Based on microarray data syntenin-a is one of the genes upregulated by 11 days post-injury. qPCR analyses confirm this upregulation of syntenin-a at 6 and 11 days after SCI (spinal cord injury), that correspond to the chroninc response phase of the spinal cord to the injury. However, no upregulation is detected during the early acute phase response (4-12h after SCI). Whole-mount in situ hybridizations validate this upregulation as there is a significant increase of cells expressing syntenin-a adjacent to the lesion site 6 days after SCI. Both neurons and glial cells upregulate the expression of syntenin-a. Next and in order to determine whether this upregulation of syntenin-a is required for locomotor function recovery after SCI the authors knocked-down this gene with morpholinos. After silencing syntenin-a both the duration of the movement and the total distance moved was significantly reduced compared to controls at 6 weeks post-SCI, suggesting an important role of syntenin-a in locomotor recovery. By performing retrograde and anterograde labelling the authors showed how there is significant decrease in the number of neurons, regrown axons and newly formed synapses at the lesion site, after knocking down syntenin-a.

After SCI in zebrafish there is an early phase of glial cell accumulation and migration to the injury site. Later, there is a second phase characterized by the formation of a glial bridge that promotes regeneration by facilitating the growth of the axons over the injury site. Syntenin-a is upregulated after 6 days post-SCI that correlates with the formation of the glial bridge supporting the idea that syntenin-a might have a role in the formation of this glial bridge and/or changes in glial morphology during this phase. In addition, as syntenin-a also plays a role in cell migration during zebrafish development it is also possible that this factor could function during glial cell migration during spinal cord regeneration.

Given the wide variety of partners and interactions in which syntenin-a may be involved it will be important to determine which specific processes mediate this beneficial effect of this protein during spinal cord regeneration.

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Francesc Cebrià

Francesc Cebrià

Francesc Cebrià

I am a Biologist and Professor at the University of Barcelona. I do my research on a fascinating animal: freshwater planarians. You can cut them in as many pieces as you want and each piece will regenerate a complete new flatworm in very few days. In this blog I will keep you updated on the latest news on the field of animal regeneration. You will be able to follow the latest research on how planarians, axolotls, newts, cnidarians and other animals are able to regenerate parts of their bodies

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