Embryonic Stem Cell-Derived Neurons as a Model System for Epigenome Maturation during Development.

DNA methylation in neurons is directly linked to neuronal genome regulation and maturation. Unlike other tissues, vertebrate neurons accumulate high levels of atypical DNA methylation in the CH sequence context (mCH) during early postnatal brain development. Here, we investigate to what extent neurons derived in vitro from both mouse and human pluripotent stem cells recapitulate in vivo DNA methylation patterns.

Adherens Junctions: Guardians of Cortical Development.

Apical radial glia comprise the pseudostratified neuroepithelium lining the embryonic lateral ventricles and give rise to the extensive repertoire of pyramidal neuronal subtypes of the neocortex. The establishment of a highly apicobasally polarized radial glial morphology is a mandatory prerequisite for cortical development as it governs neurogenesis, neural migration and the integrity of the ventricular wall. As in all epithelia, cadherin-based adherens junctions (AJs) play an obligate role in the maintenance of radial glial apicobasal polarity and neuroepithelial cohesion.

WNT5a Regulates Epithelial Morphogenesis in the Developing Choroid Plexus.

The choroid plexus (CP) is the predominant supplier of cerebral spinal fluid (CSF) and the site of the blood-CSF barrier and is thus essential for brain development and central nervous system homeostasis. Despite these crucial roles, our understanding of the molecular and cellular processes giving rise to the CPs within the ventricles of the mammalian brain is very rudimentary. Here, we identify WNT5a as an important regulator of CP development, where it acts as a pivotal factor driving CP epithelial morphogenesis in all ventricles.

An ex vivo model to quantitatively analyze cell migration in tissue.

Background: Within the developing central nervous system, the ability of cells to migrate throughout the tissue parenchyma to reach their target destination and undergo terminal differentiation is vital to normal central nervous system (CNS) development. To develop novel therapies to treat the injured CNS, it is essential that the migratory behavior of cell populations is understood. Many studies have examined the ability of individual neurons to migrate through the developing CNS, describing specific modes of migration including locomotion and somal translocation.

Neogenin Recruitment of the WAVE Regulatory Complex to Ependymal and Radial Progenitor Adherens Junctions Prevents Hydrocephalus.

Denudation of the ependyma due to loss of cell adhesion mediated by cadherin-based adherens junctions is a common feature of perinatal hydrocephalus. Junctional stability depends on the interaction between cadherins and the actin cytoskeleton. However, the molecular mechanism responsible for recruiting the actin nucleation machinery to the ependymal junction is unknown.

Neogenin recruitment of the WAVE regulatory complex maintains adherens junction stability and tension.

To maintain tissue integrity during epithelial morphogenesis, adherens junctions (AJs) must resist the mechanical stresses exerted by dynamic tissue movements. Junctional stability is dependent on actomyosin contractility within the actin ring. Here we describe a novel function for the axon guidance receptor, Neogenin, as a key component of the actin nucleation machinery governing junctional stability.

The Netrin/RGM receptor, Neogenin, controls adult neurogenesis by promoting neuroblast migration and cell cycle exit.

A comprehensive understanding of adult neurogenesis is essential for the development of effective strategies to enhance endogenous neurogenesis in the damaged brain. Olfactory interneurons arise throughout life from stem cells residing in the subventricular zone of the lateral ventricle. Neural precursors then migrate along the rostral migratory stream (RMS) to the olfactory bulb.

RGMa regulates cortical interneuron migration and differentiation.

The etiology of neuropsychiatric disorders, including schizophrenia and autism, has been linked to a failure to establish the intricate neural network comprising excitatory pyramidal and inhibitory interneurons during neocortex development. A large proportion of cortical inhibitory interneurons originate in the medial ganglionic eminence (MGE) of the ventral telencephalon and then migrate through the ventral subventricular zone, across the corticostriatal junction, into the embryonic cortex. Successful navigation of newborn interneurons through the complex environment of the ventral telencephalon is governed by spatiotemporally restricted deployment of both chemorepulsive and chemoattractive guidance cues which work in concert to create a migratory corridor.

Spinal cord neuroepithelial progenitor cells display developmental plasticity when co-cultured with embryonic spinal cord slices at different stages of development.

All neurons and glial cells of the vertebrate CNS are derived from embryonic neuroepithelial progenitor cells (NEP). Distinct modes of radial neuronal migration, locomotion, and somal translocation have been described in the cerebral cortex, but less is known about the migratory behavior of neuroepithelial cells and their neuronal and glial descendants in the developing spinal cord. Here a novel spinal cord slice co-culture was developed to investigate the migration and differentiation potential of NEPs in the developing spinal cord.