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. 2022 Jul 7;1:kvac009. doi: 10.1093/oons/kvac009

Figure 4.

Figure 4

In silico modelling of neuronal migration dynamics upon MADM-based Cdk5r1 ablation. (A–C) Representative migration trajectories in (A) control-MADM, (B) KO-Cdk5r1-MADM and (C) Cdk5r1-MADM. (D) Normalized velocity distributions from experimental data in control-MADM (n = 4), KO-Cdk5r1-MADM (n = 3) and Cdk5r1-MADM (n = 3). (E) Model of neuron migration in control environment with corresponding resistance zones. The thickness of the arrows indicates the probability to move in any direction. The random walk bias of cells in form of directionality and force generation when cells move (arrow) and with force conservation included as a spring constant when cells do not move (spring arrow). The directionality bias is defined as 65% in pial-direction for control. (F) Model of neuron migration in global Cdk5r1 KO environment with a single resistance zone. The thickness of the arrows indicates the probability to move in any direction, here the directionality bias is defined as 51% in pial-direction. The random walk bias of cells in form of directionality and force generation when cells move (arrow) and with force conservation included as a spring constant when cells do not move (spring arrow). (G) Mixed model indicating cross interactions of Cdk5r1−/− mutant and control cells, respectively. The directionality bias is defined in pial-direction as a function of N_ctrl/N_Mut with a minimum at 51% and a maximum at 65%. The thickness of the arrows indicates the probability of the mutant neuron to move in any direction. The random walk bias of cells in form of directionality and force generation when cells move (arrow) and with force conservation included as a spring constant when cells do not move (spring arrow). (H–I) Simulation of migration trajectories in (H) control model, (I) global Cdk5r1 KO model and (J) mixed model (95% Ctrl, 5% KO). Resistant zones are indicated accordingly. (K) Normalized velocity distributions of simulation trajectories.