Complex regional pain syndrome type 1 (CRPS-1) is a chronic pain disorder that in some patients is associated with fixed dystonia. The pathogenesis of CRPS and its relation to dystonia remain... Show moreComplex regional pain syndrome type 1 (CRPS-1) is a chronic pain disorder that in some patients is associated with fixed dystonia. The pathogenesis of CRPS and its relation to dystonia remain poorly understood. Several genes (so-called DYT genes) identified in other causes of dystonia play a role in mechanisms that have been implicated in CRPS. Because different mutations in the same gene can result in diverse phenotypes, we sequenced all coding exons of the DYT1, DYT5a, DYT5b, DYT6, DYT11, DYT12, and DYT16 genes in 44 CRPS patients with fixed dystonia to investigate whether high-penetrant causal mutations play a role in CRPS. No such mutations were identified, indicating that these genes do not seem to play a major role in CRPS. Show less
Hoekstra, M.; Stitzinger, M.; Wanrooij, E.J.A. van; Michon, I.N.; Kruijt, J.K.; Kamphorst, J.T.; ... ; Kuiper, J. 2006
The decision of whether and where to cross the midline, an evolutionarily conserved line of bilateral symmetry in the central nervous system, is the first task for many newly extending axons. We... Show moreThe decision of whether and where to cross the midline, an evolutionarily conserved line of bilateral symmetry in the central nervous system, is the first task for many newly extending axons. We show that Wnt5, a member of the conserved Wnt secreted glycoprotein family, is required for the formation of the anterior of the two midline-crossing commissures present in each Drosophila hemisegment. Initial path finding of pioneering neurons across the midline in both commissures is normal in wnt5 mutant embryos; however, the subsequent separation of the early midline-crossing axons into two distinct commissures does not occur. The majority of the follower axons that normally cross the midline in the anterior commissure fail to do so, remaining tightly associated near their cell bodies, or projecting inappropriately across the midline in between the commissures. The lateral and intermediate longitudinal pathways also fail to form correctly, similarly reflecting earlier failures in pathway defasciculation. Panneural expression of Wnt5 in a wnt5 mutant background rescues both the commissural and longitudinal defects. We show that the Wnt5 protein is predominantly present on posterior commissural axons and at a low level on the anterior commissure and longitudinal projections. Finally, we demonstrate that transcriptional repression of wnt5 in AC neurons by the recently described Wnt5 receptor, Derailed, contributes to this largely posterior commissural localization of Wnt5 protein. Show less
Tetraspanins encode a large conserved family of proteins that span the membrane four times and are expressed in a variety of eukaryotic tissues. They are part of membrane complexes that are... Show moreTetraspanins encode a large conserved family of proteins that span the membrane four times and are expressed in a variety of eukaryotic tissues. They are part of membrane complexes that are involved in such diverse processes as intracellular signaling, cellular motility, metastasis, and tumor suppression. The single fly tetraspanin characterized to date, late bloomer (lbm), is expressed on the axons, terminal arbors, and growth cones of motoneurons. In embryos lacking Lbm protein, motoneurons reach their muscle targets, but initially fail to form synaptic terminals. During larval stages, however, functional contacts are formed. The newly available genomic sequence of Drosophila melanogaster indicates the existence of 34 additional members of the tetraspanin family in the fly. To address the possibility that other tetraspanins with functions that might compensate for a lack of lbm exist, we determined the expression domains of the Drosophila tetraspanin gene family members by RNA in situ analysis. We found two other tetraspanins also expressed in motoneurons and subsequently generated a small chromosomal deletion that removes all three motoneuronspecific tetraspanins. The deletion results in a significant enhancement in the lbm phenotype, indicating that the two additional motoneuron-expressed tetraspanins can, at least in part, compensate for the absence of lbm during the formation of the embryonic synapse. Show less
