Involvement of Islet-2 in the Slit signaling for axonal branching and defasciculation of the sensory neurons in embryonic zebrafish.
In Drosophila melanogaster, Slit acts as a repulsive cue for the growth cones of the commissural axons which express a receptor for Slit, Roundabout (Robo), thus preventing the commissural axons from crossing the midline multiple times. Experiments using explant culture have shown that vertebrate Slit homologues also act repulsively for growth cone navigation and neural migration, and promote branching and elongation of sensory axons. Here, we demonstrate that overexpression of Slit2 in vivo in transgenic zebrafish embryos severely affected the behavior of the commissural reticulospinal neurons (Mauthner neurons), promoted branching of the peripheral axons of the trigeminal sensory ganglion neurons, and induced defasciculation of the medial longitudinal fascicles. In addition, Slit2 overexpression caused defasciculation and deflection of the central axons of the trigeminal sensory ganglion neurons from the hindbrain entry point. The central projection was restored by either functional repression or mutation of Robo2, supporting its role as a receptor mediating the Slit signaling in vertebrate neurons. Furthermore, we demonstrated that Islet-2, a LIM/homeodomain-type transcription factor, is essential for Slit2 to induce axonal branching of the trigeminal sensory ganglion neurons, suggesting that factors functioning downstream of Islet-2 are essential for mediating the Slit signaling for promotion of axonal branching.
Yeo
Sang-Yeob
SY
Laboratory for Developmental Gene Regulation, RIKEN Brain Science Institute, 2-1, Hirosawa, Wako, Saitama 351-0198, Japan.
Miyashita
Toshio
T
Fricke
Cornelia
C
Little
Melissa H
MH
Yamada
Toshiya
T
Kuwada
John Y
JY
Huh
Tae-Lin
TL
Chien
Chi-Bin
CB
Okamoto
Hitoshi
H
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism*; D017930:Genes, Reporter; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism*; D000097905:Roundabout Proteins
D006023:Glycoproteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C490404:isl2a protein, zebrafish; C498889:robo2 protein, zebrafish; D000097905:Roundabout Proteins; C120566:slit protein, vertebrate