title: Essential roles of zebrafish rtn4/Nogo paralogues in embryonic development.
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.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Pinzón-Olejua
authors.forename: Cornelia
authors.initials: C
authors.lastname: Welte
authors.forename: Houari
authors.initials: H
authors.lastname: Abdesselem
authors.affiliation: Department of Biology, University of Konstanz, Universitätsstrasse 10, 78476 Konstanz, Germany. Edward.Malaga@uni-konstanz.de.
authors.forename: Edward
authors.initials: E
authors.lastname: Málaga-Trillo
authors.forename: Claudia Ao
authors.initials: CA
authors.lastname: Stuermer
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000196:embryology; D015536:Down-Regulation; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D000070798:Nogo Proteins; D012160:Retina / Q000196:embryology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D009185:Myelin Proteins; D000070798:Nogo Proteins; C000592544:Rtn4a protein, zebrafish; C000592545:Rtn4b protein, zebrafish; D029961:Zebrafish Proteins
references.citation: Cell. 2006 Feb 10;124(3):573-86
references.pmid: 16469703
references.citation: J Neurosci. 1984 Apr;4(4):1045-51
references.pmid: 6325602
references.citation: Cereb Cortex. 2007 Oct;17(10):2375-86
references.pmid: 17192421
references.citation: FASEB J. 2003 Jul;17(10):1238-47
references.pmid: 12832288
references.citation: Neuron. 2003 Apr 24;38(2):201-11
references.pmid: 12718855
references.citation: Dev Biol. 2007 Jan 15;301(2):578-89
references.pmid: 17157288
references.citation: J Comp Neurol. 2009 Mar 1;513(1):38-50
references.pmid: 19107846
references.citation: Mol Biol Evol. 2005 Aug;22(8):1635-48
references.pmid: 15858203
references.citation: Mol Cell Neurosci. 2009 Apr;40(4):401-9
references.pmid: 19041397
references.citation: Mar Biotechnol (NY). 2001 Nov;3(6):522-7
references.pmid: 14961324
references.citation: Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):1083-8
references.pmid: 23277570
references.citation: Neuron. 2003 Apr 24;38(2):187-99
references.pmid: 12718854
references.citation: Nat Rev Neurosci. 2010 Dec;11(12):799-811
references.pmid: 21045861
references.citation: Exp Neurol. 1963 Jan;7:46-64
references.pmid: 13965388
references.citation: Mol Biol Evol. 2011 Apr;28(4):1363-70
references.pmid: 21098000
references.citation: Nature. 2000 Jan 27;403(6768):434-9
references.pmid: 10667796
references.citation: Cell Death Differ. 2012 Jul;19(7):1096-108
references.pmid: 22193546
references.citation: Cereb Cortex. 2010 Oct;20(10):2380-90
references.pmid: 20093372
references.citation: J Neurosci. 2012 Dec 5;32(49):17788-99
references.pmid: 23223298
references.citation: J Exp Zool. 2002 Apr 15;294(1):30-46
references.pmid: 11932947
references.citation: J Neurosci. 1995 Nov;15(11):7500-8
references.pmid: 7472501
references.citation: Dev Dyn. 1995 Jul;203(3):253-310
references.pmid: 8589427
references.citation: Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2569-74
references.pmid: 21262805
references.citation: J Neurosci. 2009 May 20;29(20):6607-15
references.pmid: 19458231
references.citation: Mol Biol Evol. 2004 Jan;21(1):76-85
references.pmid: 12949137
references.citation: Science. 2005 Sep 30;309(5744):2222-6
references.pmid: 16195464
references.citation: J Comp Neurol. 1997 Jan 27;377(4):577-95
references.pmid: 9007194
references.citation: J Neurosci. 2009 Dec 9;29(49):15489-98
references.pmid: 20007473
references.citation: J Cell Physiol. 2008 Aug;216(2):303-8
references.pmid: 18330888
references.citation: J Biol Chem. 2005 Apr 1;280(13):12494-502
references.pmid: 15640160