Reelin Signaling Inactivates Cofilin to Stabilize the Cytoskeleton of Migrating Cortical Neurons

Reelin Signaling Inactivates Cofilin to Stabilize the Cytoskeleton of Migrating Cortical Neurons

Neurons are highly polarized cells. They give rise to several dendrites but only one axon. In addition, many neurons show a preferred orientation.

The student of the mammalian cerebral cortex is impressed by two phenomena pointing to a well-ordered, non-random structural organization. First, there is the arrangement of cortical neurons in layers as seen in Nissl-stained sections or in sections immunostained using layer specific markers. Second, there is an almost uniform vertical orientation of the vast majority of cortical neurons.

From a cell biological point of view numerous questions arise after this short description of cortical organization. Numerous researchers have dealt intensely with these questions during the last decades.

With the discovery of Reelin, the molecule deficient in the reeler mutant, research in this area has exploded and our understanding of layer formation in the cortex and of the different players involved has significantly improved.

Hyperphosphorylation of Tau is a hallmark of Alzheimer’s disease, suggesting an involvement of the Reelin signaling cascade in the pathology of this disorder but further work is needed to obtain a clearer picture.

Reelin-induced stabilization of the leading process, likely by the phosphorylation of cofilin, is an essential step in the proper orientation and migration directionality of late-generated cortical neurons.

future studies need to find out how Reelin in the MZ induces both branching and stabilization of the actin cytoskeleton by cofilin phosphorylation.

many other molecular players such as molecules of the tubulin cytoskeleton (e.g., Meseke et al., 2013; Förster, 2014), proneural transcription factors such as Rnd proteins (Pacary et al., 2011), and CLASP2 (Dillon et al., 2017) are also known to control the cytoskeleton of neuronal cells and extension and orientation of the leading process, migration by nuclear translocation associated with a myosin II-dependent flow of actin filaments (He et al., 2010), and eventually layer formation in the cerebral cortex.