Functional repression of Islet-2 by disruption of complex with Ldb impairs peripheral axonal outgrowth in embryonic zebrafish.
Islet-2 is a LIM/homeodomain-type transcription factor of the Islet-1 family expressed in embryonic zebrafish. Two Islet-2 molecules bind to the LIM domain binding protein (Ldb) dimers. Overexpression of the LIM domains of Islet-2 or the LIM-interacting domain of Ldb proteins prevented binding of Islet-2 to Ldb proteins in vitro and caused similar in vivo defects in positioning, peripheral axonal outgrowth, and neurotransmitter expression by the Islet-2-positive primary sensory and motor neurons as the defects induced by injection of Islet-2-specific antisense morpholino oligonucleotide. These and other experiments, i.e., mosaic analysis, coexpression of full-length Islet-2, and overexpression of the chimeric LIM domains derived from two different Islet-1 family members, demonstrated that Islet-2 regulates neuronal differentiation by forming a complex with Ldb dimers and possibly with some other Islet-2-specific cofactors.
Segawa
H
H
Laboratory for Developmental Gene Regulation, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Miyashita
T
T
Hirate
Y
Y
Higashijima
S
S
Chino
N
N
Uyemura
K
K
Kikuchi
Y
Y
Okamoto
H
H
D000818:Animals; D001369:Axons / Q000502:physiology*; D001665:Binding Sites; D004625:Embryo, Nonmammalian / Q000502:physiology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D009030:Mosaicism; D009046:Motor Neurons / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009475:Neurons, Afferent / Q000502:physiology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors; D014158:Transcription, Genetic; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D049452:Green Fluorescent Proteins