Fig. 2. Cell-autonomous impairment of the multipolar-to-bipolar transformation
within the SVZ-IZ in neurons expressing Cdk5-DN. Mixtures of CRC-Cdk5-DN
and CAG-RFP were used in different ratios for in utero electroporation of
E14.5 mouse embryos. (A,A') The distribution and
morphology of RFP-positive cells (red) were analysed in coronal sections at
E18.5. Higher magnifications of the indicated areas of 100% (a) and 50%
Cdk5-DN (b) are shown in A'. Dose-dependent disturbance of neuronal
migration by CRC-Cdk5-DN was also cell-autonomous. When only Cdk5-DN was used
(100%), RFP-positive neurons arrested within the SVZ-IZ in the multipolar
shape (arrows in A'). This result matched the phenotype of
Cdk5-/- neurons, indicating that defective Cdk5 activity
in migrating neurons caused migration arrest in a cell-autonomous manner. When
Cdk5-DN was used at 50%, migration delay was observed. RFP-positive neurons
have bipolar shape in CP but some of the RFP-positive neurons have branched
leading processes (arrows in A'b). MZ, marginal zone; CP, cortical
plate; SVZ-IZ, subventricular zone-intermediate zone; VZ, ventricular zone.
Scale bar: 100 µm. (B) Bin distribution of RFP-positive neurons at
each ratio of Cdk5-DN. The cortical mantle was divided into ten equally spaced
bins and the percentage of cells in each bin calculated.