Cysteine- and glycine-rich protein 1a is involved in spinal cord regeneration in adult zebrafish

• Published in: The European journal of neuroscience 2012-02, Vol.35 (3), p.353-365
• Main Authors: Ma, Liping, Yu, Young-Mi, Guo, Yuji, Hart, Ronald P., Schachner, Melitta
• Format: Article
• Language: English
• Subjects: Animals; Brain - anatomy & histology; Brain - physiology; Carrier Proteins - genetics; Carrier Proteins - metabolism; cysteine- and glycine-rich protein 1; Danio rerio; Freshwater; Gene Expression Profiling; Gene Expression Regulation; LIM Domain Proteins - genetics; LIM Domain Proteins - metabolism; Male; microarray; Microarray Analysis; Motor Activity - physiology; Neurons - cytology; Neurons - physiology; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; nucleus of the medial longitudinal fascicle; Recovery of Function; Spinal Cord Injuries - pathology; Spinal Cord Injuries - physiopathology; Spinal Cord Regeneration; zebrafish; Zebrafish - anatomy & histology; Zebrafish - physiology; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2011.07958.x

In contrast to mammals, adult zebrafish have the ability to regrow descending axons and gain locomotor recovery after spinal cord injury (SCI). In zebrafish, a decisive factor for successful spinal cord regeneration is the inherent ability of some neurons to regrow their axons via (re)expressing growth‐associated genes during the regeneration period. The nucleus of the medial longitudinal fascicle (NMLF) is one of the nuclei capable of regenerative response after SCI. Using microarray analysis with laser capture microdissected NMLF, we show that cysteine‐ and glycine‐rich protein (CRP)1a (encoded by the csrp1a gene in zebrafish), the function of which is largely unknown in the nervous system, was upregulated after SCI. In situ hybridization confirmed the upregulation of csrp1a expression in neurons during the axon growth phase after SCI, not only in the NMLF, but also in other nuclei capable of regeneration, such as the intermediate reticular formation and superior reticular formation. The upregulation of csrp1a expression in regenerating nuclei started at 3 days after SCI and continued to 21 days post‐injury, the longest time point studied. In vivo knockdown of CRP1a expression using two different antisense morpholino oligonucleotides impaired axon regeneration and locomotor recovery when compared with a control morpholino, demonstrating that CRP1a upregulation is an important part of the innate regeneration capability in injured neurons of adult zebrafish. This study is the first to demonstrate the requirement of CRP1a for zebrafish spinal cord regeneration. In contrast to mammals, adult zebrafish have the ability to regrow descending axons and gain locomotor recovery after spinal cord injury (SCI). In zebrafish, a decisive factor for successful spinal cord regeneration is the inherent ability of some neurons to regrow their axons via (re)expressing growth‐associated genes during the regeneration period.