title: Slit and Semaphorin signaling governed by Islet transcription factors positions motor neuron somata within the neural tube.
abstract: Motor neurons send out axons to peripheral muscles while their cell bodies remain in the ventral spinal cord. The unique configuration of motor neurons spanning the border between the CNS and PNS has been explained by structural barriers such as boundary cap (BC) cells, basal lamina and radial glia. However, mechanisms in motor neurons that retain their position have not been addressed yet. Here we demonstrate that the Islet1 (Isl1) and Islet2 (Isl2) transcription factors, which are essential for acquisition of motor neuron identity, also contribute to restrict motor neurons within the neural tube. In mice that lack both Isl1 and Isl2, large numbers of motor neurons exited the neural tube, even prior to the appearance of BC cells at the ventral exit points. Transcriptional profiling of motor neurons derived from Isl1 null embryonic stem cells revealed that transcripts of major genes involved in repulsive mechanisms were misregulated. Particularly, expression of Neuropilin1 (Npr1) and Slit2 mRNA was diminished in Islet mutant mice, and these could be target genes of the Islet proteins. Consistent with this mechanism, Robo and Slit mutations in mice and knockdown of Npr1 and Slit2 in chick embryos caused motor neurons to migrate to the periphery. Together, our study suggests that Islet genes engage Robo-Slit and Neuropilin-Semaphorin signaling in motor neurons to retain motor somata within the CNS.
authors.affiliation: School of Life Sciences, Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712, Republic of Korea.
authors.forename: Hojae
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biology, University of Nevada, Reno, NV 89557, USA.
authors.forename: Minkyung
authors.initials: M
authors.lastname: Kim
authors.affiliation: School of Life Sciences, Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712, Republic of Korea.
authors.forename: Namhee
authors.initials: N
authors.lastname: Kim
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Macfarlan
authors.affiliation: Gene Expression Laboratory and the Howard Hughes Medical Institute, The Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USA.
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Pfaff
authors.affiliation: Department of Biology, University of Nevada, Reno, NV 89557, USA.
authors.forename: Grant S
authors.initials: GS
authors.lastname: Mastick
authors.affiliation: School of Life Sciences, Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712, Republic of Korea. Electronic address: msong@gist.ac.kr.
authors.forename: Mi-Ryoung
authors.initials: MR
authors.lastname: Song
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D060850:LIM-Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D054259:Neural Tube / Q000378:metabolism*; D039942:Neuropilin-1 / Q000235:genetics* / Q000378:metabolism; D039961:Semaphorins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C558561:Isl2 protein, mouse; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D039961:Semaphorins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D039942:Neuropilin-1; D000098552:Slit Homolog 2 Protein
keywords: Islet1; Islet2; Motor neuron somata; Neuropilin1; Slit2
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