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OLIG1 and OLIG2 are basic-helix-loop-helix (bHLH) transcription factors expressed in the pMN domain of the spinal cord, which sequentially generates motoneurons and oligodendrocytes. In Olig1/2 double-mutant mice, motoneurons are largely eliminated, and oligodendrocyte differentiation is abolished. Lineage tracing data suggest that Olig1(-/-)2(-/-) pMN(More)
Olig2, a basic helix-loop-helix (bHLH) transcription factor, is expressed in a restricted domain of the spinal cord ventricular zone that sequentially generates motoneurons and oligodendrocytes. Just prior to oligo-dendrocyte precursor formation, the domains of Olig2 and Nkx2.2 expression switch from being mutually exclusive to overlapping, and Neurogenins1(More)
Basic helix-loop-helix (bHLH) transcription factors have been identified for neurons and their precursors but not for glial cells. We have identified two bHLH factors, Oligo1 and Oligo2, that are specifically expressed in zones of neuroepithelium from which oligodendrocyte precursors emerge, as well as in the precursors themselves. Expression of Oligo2 in(More)
One goal of regenerative medicine is to instructively convert adult cells into other cell types for tissue repair and regeneration. Although isolated examples of adult cell reprogramming are known, there is no general understanding of how to turn one cell type into another in a controlled manner. Here, using a strategy of re-expressing key developmental(More)
The molecular mechanism(s) that regulate apoptosis by caspase inhibition remain poorly understood. The main endogenous inhibitors are members of the IAP family and are exemplified by XIAP, which regulates the initiator caspase-9, and the executioner caspases-3 and -7. We report the crystal structure of the second BIR domain of XIAP (BIR2) in complex with(More)
Tyrosine hydroxylase catalyses the initial, rate-limiting step in the catecholamine biosynthetic pathway. Catecholamines, which include dopamine, noradrenaline, and adrenaline, are important neurotransmitters and hormones that regulate visceral functions, motor coordination and arousal in adults. The gene encoding tyrosine hydroxylase becomes(More)
Astrocytes constitute the most abundant cell type in the central nervous system (CNS) and play diverse functional roles, but the ontogenetic origins of this phenotypic diversity are poorly understood. We have investigated whether positional identity, a fundamental organizing principle governing the generation of neuronal subtype diversity, is also relevant(More)
The signal transduction pathways of the dopamine-D1 receptor were investigated in two cell types stably transfected with the human D1 receptor cDNA, rat pituitary GH4C1 cells (GH4-hD1), and mouse Ltk-fibroblast cells (L-hD1). In both GH4-hD1 and L-hD1 cell lines, stimulation of the dopamine-D1 receptor induced a marked increase in cAMP accumulation. In(More)
D1, a subtype of the dopamine receptors, is widely distributed in the nervous system and has been shown to be positively coupled to adenylate cyclase. Using a combination of in vitro receptor autoradiographic and in situ hybridization techniques, the present study examines the co-distribution of D1 receptor binding sites and D1 receptor mRNA in adjacent rat(More)
The ability to interconvert terminally differentiated cells could serve as a powerful tool for cell-based treatment of degenerative diseases, including diabetes mellitus. To determine which, if any, adult tissues are competent to activate an islet β cell program, we performed an in vivo screen by expressing three β cell "reprogramming factors" in a wide(More)