title: Slit/Robo1 signaling regulates neural tube development by balancing neuroepithelial cell proliferation and differentiation.
abstract: Formation of the neural tube is the morphological hallmark for development of the embryonic central nervous system (CNS). Therefore, neural tube development is a crucial step in the neurulation process. Slit/Robo signaling was initially identified as a chemo-repellent that regulated axon growth cone elongation, but its role in controlling neural tube development is currently unknown. To address this issue, we investigated Slit/Robo1 signaling in the development of chick neCollege of Life Sciences Biocentre, University of Dundee, Dundee DD1 5EH, UKural tube and transgenic mice over-expressing Slit2. We disrupted Slit/Robo1 signaling by injecting R5 monoclonal antibodies into HH10 neural tubes to block the Robo1 receptor. This inhibited the normal development of the ventral body curvature and caused the spinal cord to curl up into a S-shape. Next, Slit/Robo1 signaling on one half-side of the chick embryo neural tube was disturbed by electroporation in ovo. We found that the morphology of the neural tube was dramatically abnormal after we interfered with Slit/Robo1 signaling. Furthermore, we established that silencing Robo1 inhibited cell proliferation while over-expressing Robo1 enhanced cell proliferation. We also investigated the effects of altering Slit/Robo1 expression on Sonic Hedgehog (Shh) and Pax7 expression in the developing neural tube. We demonstrated that over-expressing Robo1 down-regulated Shh expression in the ventral neural tube and resulted in the production of fewer HNK-1(+) migrating neural crest cells (NCCs). In addition, Robo1 over-expression enhanced Pax7 expression in the dorsal neural tube and increased the number of Slug(+) pre-migratory NCCs. Conversely, silencing Robo1 expression resulted in an enhanced Shh expression and more HNK-1(+) migrating NCCs but reduced Pax7 expression and fewer Slug(+) pre-migratory NCCs were observed. In conclusion, we propose that Slit/Robo1 signaling is involved in regulating neural tube development by tightly coordinating cell proliferation and differentiation during neurulation.
authors: Key Laboratory for Regenerative Medicine of The Ministry of Education, Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632, China.
authors: Guang
authors: G
authors: Wang
authors: Yan
authors: Y
authors: Li
authors: Xiao-yu
authors: XY
authors: Wang
authors: Zhe
authors: Z
authors: Han
authors: Manli
authors: M
authors: Chuai
authors: Li-jing
authors: LJ
authors: Wang
authors: Kenneth Ka
authors: KK
authors: Ho Lee
authors: Jian-guo
authors: JG
authors: Geng
authors: Xuesong
authors: X
authors: Yang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002642:Chick Embryo; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D054259:Neural Tube / Q000196:embryology* / Q000378:metabolism; D046569:Neuroepithelial Cells / Q000378:metabolism / Q000502:physiology*; D054261:Neurulation / Q000235:genetics / Q000502:physiology; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein