DCC-Mediated Dab1 Phosphorylation Participates in the Multipolar-to-Bipolar Transition of Migrating Neurons
Jian-Hua Zhang,
Yi-Fei Zhao,
Xiao-Xiao He,
Yang Zhao,
Zi-Xuan He,
Lei Zhang,
Ying Huang,
Yu-Bing Wang,
Ling Hu,
Lin Liu,
Hua-Li Yu,
Jia-Hui Xu,
Ming-Ming Lai,
Dong-Dong Zhao,
Lei Cui,
Wei-Xiang Guo,
Wen-Cheng Xiong,
Yu-Qiang Ding,
Xiao-Juan Zhu
Affiliations
Jian-Hua Zhang
Key Laboratory of Molecular Epigenetics, Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130021, China
Yi-Fei Zhao
Key Laboratory of Molecular Epigenetics, Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130021, China
Xiao-Xiao He
Key Laboratory of Molecular Epigenetics, Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130021, China
Yang Zhao
Key Laboratory of Molecular Epigenetics, Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130021, China
Zi-Xuan He
Key Laboratory of Molecular Epigenetics, Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130021, China
Lei Zhang
Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, and Department of Anatomy and Neurobiology, Collaborative Innovation Center for Brain Science, Tongji University School of Medicine, Shanghai 200092, China
Ying Huang
Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, and Department of Anatomy and Neurobiology, Collaborative Innovation Center for Brain Science, Tongji University School of Medicine, Shanghai 200092, China
Yu-Bing Wang
Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, and Department of Anatomy and Neurobiology, Collaborative Innovation Center for Brain Science, Tongji University School of Medicine, Shanghai 200092, China
Ling Hu
Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, and Department of Anatomy and Neurobiology, Collaborative Innovation Center for Brain Science, Tongji University School of Medicine, Shanghai 200092, China
Lin Liu
Key Laboratory of Molecular Epigenetics, Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130021, China
Hua-Li Yu
Key Laboratory of Molecular Epigenetics, Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130021, China
Jia-Hui Xu
Key Laboratory of Molecular Epigenetics, Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130021, China
Ming-Ming Lai
Key Laboratory of Molecular Epigenetics, Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130021, China
Dong-Dong Zhao
Key Laboratory of Molecular Epigenetics, Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130021, China
Lei Cui
Key Laboratory of Molecular Epigenetics, Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130021, China
Wei-Xiang Guo
State Key Laboratory for Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
Wen-Cheng Xiong
Department of Neurology, Georgia Regents University, Augusta, GA, USA; Department of Neuroscience, School of Medicine, Case Western Reserve University, Cleveland, OH 44120, USA
Yu-Qiang Ding
Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, and Department of Anatomy and Neurobiology, Collaborative Innovation Center for Brain Science, Tongji University School of Medicine, Shanghai 200092, China; Institute of Brain Sciences, Fudan University, Shanghai 200031, China; Corresponding author
Xiao-Juan Zhu
Key Laboratory of Molecular Epigenetics, Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130021, China; Corresponding author
Summary: Newborn neurons undergo inside-out migration to their final destinations during neocortical development. Reelin-induced tyrosine phosphorylation of disabled 1 (Dab1) is a critical mechanism controlling cortical neuron migration. However, the roles of Reelin-independent phosphorylation of Dab1 remain unclear. Here, we report that deleted in colorectal carcinoma (DCC) interacts with Dab1 via its P3 domain. Netrin 1, a DCC ligand, induces Dab1 phosphorylation at Y220 and Y232. Interestingly, knockdown of DCC or truncation of its P3 domain dramatically delays neuronal migration and impairs the multipolar-to-bipolar transition of migrating neurons. Notably, the migration delay and morphological transition defects are rescued by the expression of a phospho-mimetic Dab1 or a constitutively active form of Fyn proto-oncogene (Fyn), a member of the Src-family tyrosine kinases that effectively induces Dab1 phosphorylation. Collectively, these findings illustrate a DCC-Dab1 interaction that ensures proper neuronal migration during neocortical development. : Non-Reelin-induced Dab1 phosphorylation was previously identified, but not characterized. Zhang et al. find that DCC interacts with Dab1, and DCC-mediated signaling effectively induces Dab1 phosphorylation. The DCC/Dab1 signaling complex is essential for neuronal migration, especially during the multipolar-to-bipolar transition. Keywords: Dab1, DCC, Fyn, morphological transition, netrin 1, neocortex development, neuronal migration, Reelin, tyrosine phosphorylation
