Essential roles of zebrafish rtn4/Nogo paralogues in embryonic development

Alejandro Pinzón-Olejua, Cornelia Welte, Houari Abdesselem, Edward Málaga-Trillo, Claudia A O Stuermer

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number8
JournalNeural Development
Volume9
Issue number1
DOIs
Publication statusPublished - 23 Apr 2014

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Somites
Zebrafish
Embryonic Development
Spinal Cord
Branchial Region
Morpholinos
Amino Acid Motifs
Neural Tube
Gene Duplication
Neuropil
Superior Colliculi
Brain
Jaw
Nervous System
Genes
Axons
Retina
Down-Regulation
Genome

Keywords

  • Brain and spinal cord development
  • Larval motility
  • Morpholino knockdown
  • Nogo
  • Reticulon
  • rtn4
  • Zebrafish

ASJC Scopus subject areas

  • Developmental Neuroscience

Cite this

Essential roles of zebrafish rtn4/Nogo paralogues in embryonic development. / Pinzón-Olejua, Alejandro; Welte, Cornelia; Abdesselem, Houari; Málaga-Trillo, Edward; Stuermer, Claudia A O.

In: Neural Development, Vol. 9, No. 1, 8, 23.04.2014.

Research output: Contribution to journalArticle

Pinzón-Olejua, Alejandro ; Welte, Cornelia ; Abdesselem, Houari ; Málaga-Trillo, Edward ; Stuermer, Claudia A O. / Essential roles of zebrafish rtn4/Nogo paralogues in embryonic development. In: Neural Development. 2014 ; Vol. 9, No. 1.
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AB - 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.

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