A microfluidic approach to rescue ALS motor neuron degeneration using rapamycin.

TAR DNA-binding protein-43 (TDP-43) is known to accumulate in ubiquitinated inclusions of amyotrophic lateral sclerosis affected motor neurons, resulting in motor neuron degeneration, loss of motor functions, and eventually death. Rapamycin, an mTOR inhibitor and a commonly used immunosuppressive drug, has been shown to increase the survivability of Amyotrophic Lateral Sclerosis (ALS) affected motor neurons. Here we present a transgenic, TDP-43-A315T, mouse model expressing an ALS phenotype and demonstrate the presence of ubiquitinated cytoplasmic TDP-43 aggregates with > 80% cell death by 28 days post differentiation in vitro.

Development-on-chip: in vitro neural tube patterning with a microfluidic device.

Embryogenesis is a highly regulated process in which the precise spatial and temporal release of soluble cues directs differentiation of multipotent stem cells into discrete populations of specialized adult cell types. In the spinal cord, neural progenitor cells are directed to differentiate into adult neurons through the action of mediators released from nearby organizing centers, such as the floor plate and paraxial mesoderm. These signals combine to create spatiotemporal diffusional landscapes that precisely regulate the development of the central nervous system (CNS).

Guidance of postural motoneurons requires MAPK/ERK signaling downstream of fibroblast growth factor receptor 1.

Identification of intracellular signaling pathways necessary for appropriate axon guidance is challenging because many CNS populations used to study these events contain multiple cell types. Here, we resolve this issue by using mouse embryonic stem (ES) cells that were directed to differentiate into a population of motoneurons that exclusively innervate epaxial muscles [medial median motor column (MMCm) motoneurons]. These ES cell-derived MMCm motoneurons, like their endogenous counterparts, express fibroblast growth factor receptor 1 (FGFR1) and selectively extend axons toward the epaxial trophin FGF8.

Easy and rapid differentiation of embryonic stem cells into functional motoneurons using sonic hedgehog-producing cells.

Directing embryonic stem (ES) cells to differentiate into functional motoneurons has proven to be a strong technique for studying neuronal development as well as being a potential source of tissue for cell replacement therapies involving spinal cord disorders. Unfortunately, one of the mitogenic factors (i.e.

Motoneurons derived from embryonic stem cells express transcription factors and develop phenotypes characteristic of medial motor column neurons.

Embryonic stem (ES) cells differentiate into functional motoneurons when treated with a sonic hedgehog (Shh) agonist and retinoic acid (RA). Whether ES cells can be directed to differentiate into specific subtypes of motoneurons is unknown. We treated embryoid bodies generated from HBG3 ES cells with a Shh agonist and RA for 5 d in culture to induce motoneuron differentiation.