Saud K, Cánovas J, Lopez C I, Berndt F A, López E, Maass J C, Barriga A, Kukuljan M
Program in Physiology and Biophysics, Institute for Biomedical Sciences, and Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
Program in Physiology and Biophysics, Institute for Biomedical Sciences, and Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de Chile, Santiago, Chile; Department of Otolaryngology, Hospital Clínico Universidad de Chile, Santiago, Chile; Department of Surgery, Faculty of Medicine Clínica Alemana-Universidad del Desarrollo, Santiago, Chile.
Int J Dev Neurosci. 2017 Apr;57:1-11. doi: 10.1016/j.ijdevneu.2016.12.006. Epub 2016 Dec 26.
The development of the cerebral cortex requires the coordination of multiple processes ranging from the proliferation of progenitors to the migration and establishment of connectivity of the newborn neurons. Epigenetic regulation carried out by the COREST/LSD1 complex has been identified as a mechanism that regulates the development of pyramidal neurons of the cerebral cortex. We now identify the association of the multifunctional RNA-binding protein SFPQ to LSD1 during the development of the cerebral cortex. In vivo reduction of SFPQ dosage by in utero electroporation of a shRNA results in impaired radial migration of newborn pyramidal neurons, in a similar way to that observed when COREST or LSD1 expressions are decreased. Diminished SFPQ expression also associates to decreased proliferation of progenitor cells, while it does not affect the acquisition of neuronal fate. These results are compatible with the idea that SFPQ, plays an important role regulating proliferation and migration during the development of the cerebral cortex.
大脑皮层的发育需要多个过程的协调,从祖细胞的增殖到新生神经元的迁移和连接的建立。由COREST/LSD1复合物进行的表观遗传调控已被确定为一种调节大脑皮层锥体神经元发育的机制。我们现在确定了多功能RNA结合蛋白SFPQ在大脑皮层发育过程中与LSD1的关联。通过子宫内电穿孔shRNA在体内降低SFPQ剂量会导致新生锥体神经元的放射状迁移受损,这与COREST或LSD1表达降低时观察到的情况类似。SFPQ表达的减少也与祖细胞增殖的减少相关,而它不影响神经元命运的获得。这些结果与SFPQ在大脑皮层发育过程中调节增殖和迁移方面发挥重要作用的观点一致。