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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 thatmore » over-expressing Robo1 down-regulated Shh expression in the ventral neural tube and resulted in the production of fewer HNK-1{sup +} migrating neural crest cells (NCCs). In addition, Robo1 over-expression enhanced Pax7 expression in the dorsal neural tube and increased the number of Slug{sup +} pre-migratory NCCs. Conversely, silencing Robo1 expression resulted in an enhanced Shh expression and more HNK-1{sup +} migrating NCCs but reduced Pax7 expression and fewer Slug{sup +} 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. - Highlights: ► The role of Slit/Robo1 signaling was investigated with chick and mouse models. ► Disturbance of Slit/Robo1 signaling resulted in neural tube defects. ► Slit/Robo1 signaling regulated the proliferation of neural tube cells. ► Slit/Robo1 signaling modulated the differentiation of neural tube cells. ► Slit/Robo1 signaling balanced the proliferation and differentiation of neural tube.« less

Authors:
; ;  [1];  [2];  [3];  [2];  [4];  [2];  [5];  [1]
  1. Key Laboratory for Regenerative Medicine of The Ministry of Education, Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632 (China)
  2. Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510224 (China)
  3. College of Life Sciences Biocentre, University of Dundee, Dundee DD1 5EH (United Kingdom)
  4. Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin (Hong Kong)
  5. (United States)
Publication Date:
OSTI Identifier:
22278233
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 319; Journal Issue: 8; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; ELONGATION; MONOCLONAL ANTIBODIES; NERVE CELLS; RECEPTORS; SIGNALS; SPINAL CORD; TRANSGENIC MICE

Citation Formats

Wang, Guang, Li, Yan, Wang, Xiao-yu, Han, Zhe, Chuai, Manli, Wang, Li-jing, Ho Lee, Kenneth Ka, Geng, Jian-guo, E-mail: jgeng@umich.edu, Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109, and Yang, Xuesong, E-mail: yang_xuesong@126.com. Slit/Robo1 signaling regulates neural tube development by balancing neuroepithelial cell proliferation and differentiation. United States: N. p., 2013. Web. doi:10.1016/J.YEXCR.2013.02.011.
Wang, Guang, Li, Yan, Wang, Xiao-yu, Han, Zhe, Chuai, Manli, Wang, Li-jing, Ho Lee, Kenneth Ka, Geng, Jian-guo, E-mail: jgeng@umich.edu, Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109, & Yang, Xuesong, E-mail: yang_xuesong@126.com. Slit/Robo1 signaling regulates neural tube development by balancing neuroepithelial cell proliferation and differentiation. United States. doi:10.1016/J.YEXCR.2013.02.011.
Wang, Guang, Li, Yan, Wang, Xiao-yu, Han, Zhe, Chuai, Manli, Wang, Li-jing, Ho Lee, Kenneth Ka, Geng, Jian-guo, E-mail: jgeng@umich.edu, Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109, and Yang, Xuesong, E-mail: yang_xuesong@126.com. Wed . "Slit/Robo1 signaling regulates neural tube development by balancing neuroepithelial cell proliferation and differentiation". United States. doi:10.1016/J.YEXCR.2013.02.011.
@article{osti_22278233,
title = {Slit/Robo1 signaling regulates neural tube development by balancing neuroepithelial cell proliferation and differentiation},
author = {Wang, Guang and Li, Yan and Wang, Xiao-yu and Han, Zhe and Chuai, Manli and Wang, Li-jing and Ho Lee, Kenneth Ka and Geng, Jian-guo, E-mail: jgeng@umich.edu and Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109 and Yang, Xuesong, E-mail: yang_xuesong@126.com},
abstractNote = {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{sup +} migrating neural crest cells (NCCs). In addition, Robo1 over-expression enhanced Pax7 expression in the dorsal neural tube and increased the number of Slug{sup +} pre-migratory NCCs. Conversely, silencing Robo1 expression resulted in an enhanced Shh expression and more HNK-1{sup +} migrating NCCs but reduced Pax7 expression and fewer Slug{sup +} 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. - Highlights: ► The role of Slit/Robo1 signaling was investigated with chick and mouse models. ► Disturbance of Slit/Robo1 signaling resulted in neural tube defects. ► Slit/Robo1 signaling regulated the proliferation of neural tube cells. ► Slit/Robo1 signaling modulated the differentiation of neural tube cells. ► Slit/Robo1 signaling balanced the proliferation and differentiation of neural tube.},
doi = {10.1016/J.YEXCR.2013.02.011},
journal = {Experimental Cell Research},
number = 8,
volume = 319,
place = {United States},
year = {Wed May 01 00:00:00 EDT 2013},
month = {Wed May 01 00:00:00 EDT 2013}
}