Polarity Regulation in Migrating Neurons in the Cortex

Abstract

The formation of the cerebral cortex requires migration of billions of cells from their birth position to their final destination. A motile cell must have internal polarity in order to move in a specified direction. Locomotory polarity requires the coordinated polymerization of cytoskeletal elements such as microtubules and actin combined with regulated activities of the associated molecular motors. This review is focused on migrating neurons in the developing cerebral cortex, which need to attain internal polarity in order to reach their proper target. The position and dynamics of the centrosome plays an important function in this directed motility. We highlight recent interesting findings connecting polarity proteins with neuronal migration events regulated by the microtubule-associated molecular motor, cytoplasmic dynein.

Local Application of Neurotrophins Specifies Axons Through Inositol 1,4,5-Trisphosphate, Calcium, and Ca 2+ /Calmodulin–Dependent Protein Kinases

“…Axon specification seems to occur during the transition from multipolar to bipolar morphologies in the IZ. We believe that this transition reflects neuronal polarization in vivo, which has been described previously (22,23,58,60,62).…”

“…These multipolar neurons subsequently transform to exhibit a bipolar morphology with a leading and a trailing process (bipolar neurons) and migrate along the radial fibers of the progenitor cells toward the cortical plate (CP) (6,58,60,61). Cultured cortical neurons specify axons in a manner similar to that observed in hippocampal pyramidal neurons (6,62). RT-PCR analysis revealed that CaMKK was expressed in multipolar neurons ( fig.…”

“…Thus, the Ca 2+ -CaMKK-CaMKI pathway appears to play a critical role in axon specification downstream of NT-3. CaMKI promotes axon elongation through microtubule affinity regulating kinase 2 (MARK2) (50), which has been implicated in axon specification in the stochastic model (62,68). MARK2 belongs to the SAD kinase family and appears to regulate microtubule dynamics through phosphorylation of MAPs (69).…”

Distinct temporal hierarchies in membrane and cytoskeleton dynamics precede the morphological polarization of developing neurons

“…In vivo the situation is more complex because bipolar neurons typically migrate and it is difficult to distinguish polarity events needed to support directed migration, including changes in MT and actin dynamics (Reiner and Sapir, 2009), from those specifying axon-dendritic polarity.…”

Loss of CDK5RAP2 affects neural but not non-neural mESC differentiation into cardiomyocytes

“…35 This not only applies to neural progenitors where, e.g., the apical-basal polarity is key for sustaining interkinetic nuclear migration and thus maintaining the neural progenitor pool during neocortical development, 36, 37 but also to postmitotic cells such as neurons. 38 Given the current model that CDK5RAP2 mutations cause microcephaly not only via the temporarily increased differentiation of stem cells, but also through a premature shift from symmetric to asymmetric cell divisions and thus premature neurogenesis, we applied a protocol that enables spontaneous mESC differentiation after withdrawal of mLIF. We hereby investigated whether Cdk5rap2-depleted mESC generally tend to differentiate prematurely or if this is specific for neural differentiation.…”