Neuronal Migration: An Overview of Modes, Molecular Mechanisms and Model Systems

Abstract

A century ago, Santiago Ramón y Cajal had already postulated that neurons born in specific proliferative zones have to migrate to ensure correct neocortical layering. Today we know that neuronal migration is a common phenomenon in many brain regions and that neurons are often born micrometres to centimetres away from the place they fulfil their function. Mutations that lead to defects in neuronal migration can have devastating consequences like lissencephaly, autism and schizophrenia in humans. With these conditions in mind, neuronal migration has been an area of intense research for more than 50 years. Additionally, neuronal migration phenomena are outstanding models to understand basic themes in cell biology. The rodent neocortex has been a very popular system to study different modes of neuronal migration. More recently, additional model tissues and organisms have been examined, which help to further expand our knowledge. The authors provide an overview on different migratory modes and then focus on the cell biology that enables migration in different contexts. They further discuss some experimental challenges that need to be overcome in order to understand neuronal migration in even more depth. Key Concepts: Actomyosin and microtubules play active roles in neuronal migration. Their exact roles depend on cellular context. Endo‐ and exocytosis of adhesion molecules are crucial for cell–cell and cell–substrate adhesion during migration. Extracellular matrix proteins are important guidance cues for neuronal migration. Neuronal migration is a widespread phenomenon in the central nervous system. The advancement of modern light microscopy should be embraced to observe neuronal migration modes in intact developing organism. Two basic modes of migration exist: radial and tangential migration.

Neuronal Migration and Lamination in the Vertebrate Retina

“…Given that neurons are frequently born away from the position at which they later function, they have to move to their final layer through the developing tissue. Newborn neurons can take on complex migration routes to their final destination using different cytoskeleton components and modes of cell migration to navigate the developing tissue (Kriegstein and Noctor, 2004 ; Cooper, 2013 ; Icha and Norden, 2014 ). In addition, due to the fact that cell proliferation, migration and differentiation often occur in parallel and can thus influence each other, they need to be precisely orchestrated (Ge et al, 2006 ; Nguyen et al, 2006 ; Mairet-Coello et al, 2012 ; Rodriguez et al, 2012 ).…”

“…Neuronal migration has been most extensively studied in ex vivo cultures and organotypic slices of the cerebral neocortex and the cerebellum of rodents. The phenomenon of neuronal migration in the cerebral neocortex has been reviewed in depth elsewhere (Nadarajah and Parnavelas, 2002 ; Cooper, 2013 ; Icha and Norden, 2014 ; Hatanaka et al, 2016 ). Thus, here we only summarize key features of neuronal migration in the cerebral neocortex but focus on retinal neuronal migration and how it aids the generation of retinal wiring.…”

“…At earlier stages of cortical development, neurons radially migrate within the tissue through somal translocation (Morest, 1970a ; Nadarajah et al, 2001 ; Nadarajah and Parnavelas, 2002 ). Neurons migrating via this mode, exhibit either a unipolar or bipolar morphology and use their basal attachment to translocate their nucleus and other organelles (Nadarajah and Parnavelas, 2002 ; Cooper, 2013 ; Icha and Norden, 2014 ). As the cerebral neocortex thickens during development, some neurons attach to the radially oriented progenitor cells also known as radial glial cells.…”