Essential roles of zebrafish rtn4/Nogo paralogues in embryonic development

Neural Development

Claudia AO Stuermer³  Edward Málaga-Trillo¹  Houari Abdesselem²  Cornelia Welte³  Alejandro Pinzón-Olejua³ 

[1] Universidad Peruana Cayetano Heredia, Facultad de Ciencias y Filosofía, Laboratorios de Investigación y Desarrollo, Av. Honorio Delgado 430, Lima 31, Perú;Department of Immunology and Microbiology, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Huwar Street, 24144 Doha, Qatar;Department of Biology, University of Konstanz, Universitätsstrasse 10, 78476 Konstanz, Germany

关键词: Zebrafish;    rtn4;    Reticulon;    Nogo;    Morpholino knockdown;    Larval motility;    Brain and spinal cord development;   

Others  :  802985
DOI  :  10.1186/1749-8104-9-8

 received in 2013-07-18, accepted in 2014-03-25,  发布年份 2014

【 摘 要 】

Background

As a consequence of gene/genome duplication, the RTN4/Nogo gene has two counterparts in zebrafish: rtn4a and rtn4b. The shared presence of four specific amino acid motifs—M1 to M4—in the N-terminal region of mammalian RTN4, and zebrafish Rtn4b suggests that Rtn4b is the closest homologue of mammalian Nogo-A.

Results

To explore their combined roles in zebrafish development, we characterized the expression patterns of rtn4a and rtn4b in a comparative manner and performed morpholino-mediated knockdowns. Although both genes were coexpressed in the neural tube and developing brain at early stages, they progressively acquired distinct expression domains such as the spinal cord (rtn4b) and somites (rtn4a). Downregulation of rtn4a and rtn4b caused severe brain abnormalities, with rtn4b knockdown severely affecting the spinal cord and leading to immobility. In addition, the retinotectal projection was severely affected in both morphants, as the retina and optic tectum appeared smaller and only few retinal axons reached the abnormally reduced tectal neuropil. The neuronal defects were more persistent in rtn4b morphants. Moreover, the latter often lacked pectoral fins and lower jaws and had malformed branchial arches. Notably, these defects led to larval death in rtn4b, but not in rtn4a morphants.

Conclusions

In contrast to mammalian Nogo-A, its zebrafish homologues, rtn4a and particularly rtn4b, are essential for embryonic development and patterning of the nervous system.

【 授权许可】

   
2014 Pinzón-Olejua et al.; licensee BioMed Central Ltd.

【 图 表 】

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