N-cadherin mediates retinal lamination, maintenance of forebrain compartments and patterning of retinal neurites.
The complex, yet highly ordered and predictable, structure of the neural retina is one of the most conserved features of the vertebrate central nervous system. In all vertebrate classes, retinal neurons are organized into laminae with each neuronal class adopting specific morphologies and patterns of connectivity. Using genetic analyses in zebrafish, we demonstrate that N-cadherin (Ncad) has several distinct and crucial functions during the establishment of retinal organization. Although the location of cell division is disorganized in embryos with reduced or no Ncad function, different classes of retinal neurons are generated. However, these neurons fail to organize into correct laminae, most probably owing to compromised adhesion between retinal cells. In addition, amacrine cells exhibit exuberant and misdirected outgrowth of neurites that contributes to severe disorganization of the inner plexiform layer. Retinal ganglion cells also exhibit defects in process outgrowth, with axons exhibiting fasciculation defects and adopting incorrect ipsilateral trajectories. At least some of these defects are likely to be due to a failure to maintain compartment boundaries between eye, optic nerve and brain. Although in vitro studies have implicated Fgf receptors in modulating the axon outgrowth promoting properties of Ncad, most aspects of the Ncad mutant phenotype are not phenocopied by treatments that block Fgf receptor function.
Masai
Ichiro
I
Masai Initiative Research Unit, The Institute of Physical and Chemical Research (RIKEN), Hirosawa 2-1, Wako-shi, Saitama 351-0198, Japan. imasai@postman.riken.go.jp
Lele
Zsolt
Z
Yamaguchi
Masahiro
M
Komori
Atsuko
A
Nakata
Asuka
A
Nishiwaki
Yuko
Y
Wada
Hironori
H
Tanaka
Hideomi
H
Nojima
Yasuhiro
Y
Hammerschmidt
Matthias
M
Wilson
Stephen W
SW
Okamoto
Hitoshi
H
D022005:Adherens Junctions / Q000378:metabolism; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D019521:Body Patterning; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002455:Cell Division; D018076:DNA, Complementary / Q000235:genetics; D009154:Mutation; D009474:Neurons / Q000166:cytology; D016548:Prosencephalon / Q000196:embryology* / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; D018076:DNA, Complementary; D017468:Receptors, Fibroblast Growth Factor; D029961:Zebrafish Proteins