Intermediate filaments in developing neurons: Beyond structure

Neuronal development relies on a highly choreographed progression of dynamic cellular processes by which newborn neurons migrate, extend axons and dendrites, innervate their targets, and make functional synapses. Many of these dynamic processes require coordinated changes in morphology, powered by the cell's cytoskeleton. Intermediate filaments (IFs) are the third major cytoskeletal elements in vertebrate cells, but are rarely considered when it comes to understanding axon and dendrite growth, pathfinding and synapse formation. In this review, we first introduce the many new and exciting concepts of IF function, discovered mostly in non-neuronal cells. These roles include dynamic rearrangements, crosstalk with microtubules and actin filaments, mechano-sensing and -transduction, and regulation of signaling cascades. We then discuss the understudied roles of neuronally expressed IFs, with a particular focus on IFs expressed during development, such as nestin, vimentin and α-internexin. Lastly, we illustrate how signaling modulation by the unconventional IF nestin shapes neuronal morphogenesis in unexpected and novel ways. Even though the first IF knockout mice were made over 20 years ago, the study of the cell biological functions of IFs in the brain still has much room for exciting new discoveries.