ABSTRACT
During embryonic development of the mammalian cerebral cortex, postmitotic cortical neurons migrate radially from the ventricular zone to the cortical plate. Proper migration involves the correct orientation of migrating neurons and the transition from a multipolar to a mature bipolar morphology. Herein, we report that the 2 isoforms of Myosin-10 (Myo10) play distinct roles in the regulation of radial migration in the mouse cortex. We show that the full-length Myo10 (fMyo10) isoform is located in deeper layers of the cortex and is involved in establishing proper migration orientation. We also demonstrate that fMyo10-dependent orientation of radial migration is mediated at least in part by the netrin-1 receptor deleted in colorectal cancer. Moreover, we show that the headless Myo10 (hMyo10) isoform is required for the transition from multipolar to bipolar morphologies in the intermediate zone. Our study reveals divergent functions for the 2 Myo10 isoforms in controlling both the direction of migration and neuronal morphogenesis during radial cortical neuronal migration.
Subject(s)
Cell Movement/genetics , Cerebral Cortex/cytology , Cerebral Cortex/embryology , Myosins/metabolism , Neurons/physiology , Analysis of Variance , Animals , Cells, Cultured , DCC Receptor , Electroporation , Embryo, Mammalian , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , In Vitro Techniques , Ki-67 Antigen/metabolism , Mice, Inbred C57BL , Mice, Transgenic , Microtubule-Associated Proteins/metabolism , Myosins/genetics , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neurogenesis , Protein Isoforms/genetics , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolism , Tubulin/metabolism , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolismABSTRACT
Myosin X (Myo X), an unconventional myosin with a tail homology 4-band 4.1/ezrin/radixin/moesin (MyTH4-FERM) tail, is expressed ubiquitously in various mammalian tissues. In addition to the full-length Myo X (Myo X FL), a headless form is synthesized in the brain. So far, little is known about the function of this motor-less Myo X. In this study, the role of the headless Myo X was investigated in immortalized gonadotropin-releasing hormone (GnRH) neuronal cells, NLT. NLT cells overexpressing the headless Myo X formed fewer focal adhesions and spread more slowly than the wild-type NLT cells and GFP-expressing NLT cells. In chemomigration assays, the NLT cells overexpressing the headless Myo X migrated shorter distances and had fewer migratory cells compared with the control NLT cells.
