The CTNNBIP1-CLSTN1 fusion transcript regulates human neocortical development.

Fusion transcripts or RNAs have been found in both disordered and healthy human tissues and cells; however, their physiological functions in the brain development remain unknown. In the analysis of deposited RNA-sequence libraries covering early to middle embryonic stages, we identify 1,055 fusion transcripts present in the developing neocortex. Interestingly, 98 fusion transcripts exhibit distinct expression patterns in various neural progenitors (NPs) or neurons.

Single-cell transcriptomes reveal molecular specializations of neuronal cell types in the developing cerebellum.

The cerebellum is critical for controlling motor and non-motor functions via cerebellar circuit that is composed of defined cell types, which approximately account for more than half of neurons in mammals. The molecular mechanisms controlling developmental progression and maturation processes of various cerebellar cell types need systematic investigation. Here, we analyzed transcriptome profiles of 21119 single cells of the postnatal mouse cerebellum and identified eight main cell clusters.

The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice.

Cortical expansion and folding are often linked to the evolution of higher intelligence, but molecular and cellular mechanisms underlying cortical folding remain poorly understood. The hominoid-specific gene TBC1D3 undergoes segmental duplications during hominoid evolution, but its role in brain development has not been explored. Here, we found that expression of TBC1D3 in ventricular cortical progenitors of mice via in utero electroporation caused delamination of ventricular radial glia cells (vRGs) and promoted generation of self-renewing basal progenitors with typical morphology of outer radial glia (oRG), which are most abundant in primates.

Semaphorin 3A activates the guanosine triphosphatase Rab5 to promote growth cone collapse and organize callosal axon projections.

Axon guidance (pathfinding) wires the brain during development and is regulated by various attractive and repulsive cues. Semaphorin 3A (Sema3A) is a repulsive cue, inducing the collapse of axon growth cones. In the mammalian forebrain, the corpus callosum is the major commissure that transmits information flow between the two hemispheres, and contralateral axons assemble into well-defined tracts.

Alteration of fibroblast phenotype by asbestos-induced autoantibodies.

Pulmonary fibrosis is a relentlessly progressive disease for which the etiology can be idiopathic or associated with environmental or occupational exposures. There is not a clear explanation for the chronic and progressive nature of the disease, leaving treatment and prevention options limited. However, there is increasing evidence of an autoimmune component, since fibrotic diseases are often accompanied by production of autoantibodies.

Nuclear factor kappaB controls acetylcholine receptor clustering at the neuromuscular junction.

At the vertebrate neuromuscular junction (NMJ), acetylcholine receptor (AChR) clustering is stimulated by motor neuron-derived glycoprotein Agrin and requires a number of intracellular signal or structural proteins, including AChR-associated scaffold protein Rapsyn. Here, we report a role of nuclear factor kappaB (NF-kappaB), a well known transcription factor involved in a variety of immune responses, in regulating AChR clustering at the NMJ. We found that downregulating the expression of RelA/p65 subunit of NF-kappaB or inhibiting NF-kappaB activity by overexpression of mutated form of IkappaB (inhibitor kappaB), which is resistant to proteolytic degradation and thus constitutively keeps NF-kappaB inactive in the cytoplasma, impeded the formation of AChR clusters in cultured C2C12 muscle cells stimulated by Agrin.

Mechanism underlying activity-dependent insertion of TrkB into the neuronal surface.

Activity-dependent insertion of tyrosine kinase receptor type 2 (TrkB receptor) into the plasma membrane can explain, in part, the preferential effect of brain-derived neurotrophic factor (BDNF) on active neurons; however, the detailed cellular and molecular mechanisms underlying this process are still unclear. In our study, we developed a fluorescence ratiometric assay for surface TrkB receptors to investigate the mechanisms of recruitment of TrkB to the plasma membrane following chemical long-term potentiation (cLTP) induction. We found that, in hippocampal neurons, the effect of cLTP-induced TrkB surface-recruitment occurred predominantly on neurites with rapid kinetics (t(1/2) of approximately 2.

GDNF isoform affects intracellular trafficking and secretion of GDNF in neuronal cells.

Glial cell line derived neurotrophic factor (GDNF) plays a critical role in central and peripheral neuron survival and function. In human and rodents, GDNF exists in an alternative spliced isoform (GDNF Delta 78), which has a 78 bp deletion in the pro-region of the GDNF encoding sequence. Whether the GDNF isoform affects GDNF function is unknown.

Asbestos-induced autoimmunity in C57BL/6 mice.

Environmental impacts on autoimmunity have significant public health implications. Epidemiological studies have shown associations between exposure to airborne silicates, such as crystalline silica or asbestos, and autoimmunity, but the etiology remains unclear. The purpose of this study was to test the hypothesis that asbestos could lead to a specific pattern of autoantibodies and pathology indicative of systemic autoimmune disease (SAID).

PERK eIF2alpha kinase regulates neonatal growth by controlling the expression of circulating insulin-like growth factor-I derived from the liver.

Humans afflicted with the Wolcott-Rallison syndrome and mice deficient for PERK (pancreatic endoplasmic reticulum eIF2alpha kinase) show severe postnatal growth retardation. In mice, growth retardation in Perk-/- mutants is manifested within the first few days of neonatal development. Growth parameters of Perk-/- mice, including comparison of body weight to length and organ weights, are consistent with proportional dwarfism.

The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas.

Phosphorylation of eukaryotic initiation factor 2 alpha (eIF-2 alpha) is typically associated with stress responses and causes a reduction in protein synthesis. However, we found high phosphorylated eIF-2 alpha (eIF-2 alpha[P]) levels in nonstressed pancreata of mice. Administration of glucose stimulated a rapid dephosphorylation of eIF-2 alpha.