Individual spinal motor neuron identities are specified in large part by the intrinsic repertoire of transcription factors expressed by undifferentiated progenitors and maturing neurons. It is shown here that the transcription factor AML1/Runx1 (Runx1) is expressed in selected spinal motor neuron subtypes after the onset of differentiation and is both necessary and sufficient to suppress intern...

Scientific evidence is emerging to indicate that motor neuron injury in motor neuron disease may reflect a complex interplay between genetic factors, oxidative stress, and imbalance of the glutamatergic excitatory control of motor neurons, which may result in damage to critical target proteins and organelles. The relative importance of these factors is likely to vary in different subgroups of p...

Background: The failure of regeneration after spinal cord injury (SCI) has been attributed to axonal demyelination and neuronal death. Cellular replacement and white matter regeneration are both necessary for SCI repair. In this study, we evaluated the co-transplantation of olfactory ensheathing cells (OEC) and embryonic stem (ES) cell-derived motor neurons (ESMN) on contused SCI. Methods: OEC...

In adult zebrafish, relatively quiescent progenitor cells show lesion-induced generation of motor neurons. Developmental motor neuron generation from the spinal motor neuron progenitor domain (pMN) sharply declines at 48 hours post-fertilisation (hpf). After that, mostly oligodendrocytes are generated from the same domain. We demonstrate here that within 48 h of a spinal lesion or specific gene...

The identity of motor neurons diverges markedly at different rostrocaudal levels of the spinal cord, but the signals that specify their fate remain poorly defined. We show that retinoid receptor activation in newly generated spinal motor neurons has a crucial role in specifying motor neuron columnar subtypes. Blockade of retinoid receptor signaling in brachial motor neurons inhibits lateral mot...

The precision with which motor neurons innervate target muscles depends on a regulatory network of Hox transcription factors that translates neuronal identity into patterns of connectivity. We show that a single transcription factor, FoxP1, coordinates motor neuron subtype identity and connectivity through its activity as a Hox accessory factor. FoxP1 is expressed in Hox-sensitive motor columns...

Mutations in Sigma 1 receptor (SIGMAR1) have been previously identified in patients with amyotrophic lateral sclerosis and disruption of Sigmar1 in mouse leads to locomotor deficits. However, cellular mechanisms underlying motor phenotypes in human and mouse with disturbed SIGMAR1 function have not been described so far. Here we used a combination of in vivo and in vitro approaches to investiga...

Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cel...