Figure 8.
Schematic presentation of the results. A–E, In utero electroporation results. F, An integrated model of the role of MARK2 during radial migration. A, The normal route of radial neuronal migration initiates with neurons born in the VZ, which migrate toward the IZ. They adopt a multipolar morphology, and later, the neurons change their morphology to bipolar, and centrosomal movement (black circle, arrowhead) is tightly regulated. The majority of neurons reach the CP. This program was evident in the case of electroporating control shRNA or GFP-expression plasmid. B, In utero electroporation of MARK2 shRNA results in inhibition of neuronal migration. Many neurons are stalled in the IZ border exhibiting a multipolar morphology. The motility of centrosome in these neurons is abnormal. Some neurons exhibit abnormal morphology. C, The reduction in neuronal migration by MARK2 shRNA is partially rescued by NeuroD-MARK2. In addition, MARK2 kinase activity was modulated by overexpression of MARK2-KD or PAK5-KD, resulting in partial neuronal migration inhibition. D, Addition of MARK2R KD to MARK2 shRNA allowed transition from the multipolar to the bipolar stage but did not rescue the migration phenotype. E, Increased expression of MARK2 at early stages results in round neurons, which lost their polarity. F, Balanced MARK2 activity is needed in several steps along radial migration. (1) Low levels of MARK2 are required for cells to migrate through the IZ. If MARK2 levels are elevated, cells will lose their polarity and stall in the IZ. Reduced levels of MARK2 will cause cells to stall in the IZ boundary with multipolar morphology. (2) The multipolar-to-bipolar transition does not require an active kinase. (3) MARK2 kinase activity is essential for proper migration and centrosome motility.