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Developing Spinal Cord (developing + spinal_cord)
Selected AbstractsNeural precursor cells from a fatal human motoneuron disease differentiate despite aberrant gene expressionDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2007Niklas Pakkasjärvi Abstract Precursor cells of the human central nervous system can be cultured in vitro to reveal pathogenesis of diseases or developmental disorders. Here, we have studied the biology of neural precursor cells (NPCs) from patients of lethal congenital contracture syndrome (LCCS), a severe motoneuron disease leading to prenatal death before the 32nd gestational week. LCCS fetuses are immobile because of a motoneuron defect, seen as degeneration of the anterior horn and descending tracts of the developing spinal cord. The genetic defect for the syndrome is unknown. We show that NPCs isolated postmortem from LCCS fetuses grow and are maintained in culture, but display increased cell cycle activity. Global transcript analysis of undifferentiated LCCS precursor cells present with changes in EGF-related signaling when compared with healthy age-matched human controls. Further, we show that LCCS-derived NPCs differentiate into cells of neuronal and glial lineage and that the initial differentiation is not accompanied by overt apoptosis. Cells expressing markers Islet-1 and Hb9 are also generated from the LCCS NPCs, suggesting that the pathogenic mechanism of LCCS does not directly affect the differentiation capacity or survival of the cells, but the absence of motoneurons in LCCS may be caused by a noncell autonomous mechanism. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007 [source] Changes within maturing neurons limit axonal regeneration in the developing spinal cordDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2006Murray Blackmore Abstract Embryonic birds and mammals display a remarkable ability to regenerate axons after spinal injury, but then lose this ability during a discrete developmental transition. To explain this transition, previous research has emphasized the emergence of myelin and other inhibitory factors in the environment of the spinal cord. However, research in other CNS tracts suggests an important role for neuron-intrinsic limitations to axon regeneration. Here we re-examine this issue quantitatively in the hindbrain-spinal projection of the embryonic chick. Using heterochronic cocultures we show that maturation of the spinal cord environment causes a 55% reduction in axon regeneration, while maturation of hindbrain neurons causes a 90% reduction. We further show that young neurons transplanted in vivo into older spinal cord can regenerate axons into myelinated white matter, while older axons regenerate poorly and have reduced growth cone motility on a variety of growth-permissive ligands in vitro, including laminin, L1, and N-cadherin. Finally, we use video analysis of living growth cones to directly document an age-dependent decline in the motility of brainstem axons. These data show that developmental changes in both the spinal cord environment and in brainstem neurons can reduce regeneration, but that the effect of the environment is only partial, while changes in neurons by themselves cause a nearly complete reduction in regeneration. We conclude that maturational events within neurons are a primary cause for the failure of axon regeneration in the spinal cord. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Symposium 8: Regulation of Oligodendrocyte DevelopmentJOURNAL OF NEUROCHEMISTRY, Issue 2002R. H. Miller Oligodendrocyte precursors arise in restricted regions of the developing neuroepithelium due to local signals that include sonic hedgehog. In the spinal cord the founder cells of the oligodendrocyte lineage develop in a specific domain of the ventral ventricular zone. These cells or their progeny subsequently migrate long distances to populate the entire spinal cord and myelinate axons in the peripheral presumptive white matter. The majority of migration in the oligodendrocyte lineage is accomplished by immature precursors, which then stop, proliferate and differentiate in the appropriate location. Several distinct mechanisms appear to regulate this migration. The initial dispersal of cells from the ventral ventricular zone is guided by chemorepellent cues including netrin-1 present in the ventral ventricular domain. Migratory precursors are arrested in particular locations within the developing spinal cord as the result of the localized expression of the chemokine, CXCL1 by astrocytes. This chemokine, signalling through the CXCR2 receptor combines with PDGF to inhibit cell migration and enhance cell proliferation thereby facilitating the local expansion of the oligodendrocyte lineage and myelination of all relevant axons. [source] Identification of genes up-regulated by retinoic-acid-induced differentiation of the human neuronal precursor cell line NTERA-2 cl.D1JOURNAL OF NEUROCHEMISTRY, Issue 3 2001Frank Leypoldt The human teratocarcinoma cell line NTERA-2 cl.D1 (NT2 cells) can be induced with retinoic acid and cell aggregation to yield postmitotic neurones. This seems to model the in vivo situation, as high concentrations of retinoic acid, retinoic acid binding proteins, and receptors have been detected in the embryonic CNS and the developing spinal cord suggesting a role for retinoic acid in neurogenesis. Suppression subtractive hybridization was used to detect genes up-regulated by this paradigm of neuronal differentiation. Microfibril-associated glycoprotein 2 was found to be drastically up-regulated and has not been implicated in neuronal differentiation before. Suppression subtractive hybridization also identified DYRK4, a homologue of the Drosophila gene minibrain. Minibrain mutations result in specific defects in the development of the fly central nervous system. In adult rats, DYRK4 is only expressed in testis, but our results suggest an additional role for DYRK4 in neuronal differentiation. We have shown that suppression subtractive hybridization in conjunction with an efficient screening procedure is a valuable tool to produce a repertoire of differentially expressed genes and propose a new physiological role for several identified genes and expressed sequence tags. [source] Wnt-3a and Wnt-3 differently stimulate proliferation and neurogenesis of spinal neural precursors and promote neurite outgrowth by canonical signalingJOURNAL OF NEUROSCIENCE RESEARCH, Issue 14 2010Monica D. David Abstract Wnt factors regulate neural stem cell development and neuronal connectivity. Here we investigated whether Wnt-3a and Wnt-3, expressed in the developing spinal cord, regulate proliferation and the neuronal differentiation of spinal cord neural precursors (SCNP). Wnt-3a promoted a sustained increase of SCNP proliferation and decreased the expression of cyclin-dependent kinase inhibitors. In contrast, Wnt-3 transiently enhanced SCNP proliferation and increased neurogenesis through ,-catenin signaling. Furthermore, both Wnt-3a and Wnt-3 stimulated neurite outgrowth in SCNP-derived neurons through ,-catenin- and TCF4-dependent transcription. Glycogen synthase kinase-3, inhibitors mimicked Wnt signaling and promoted neurite outgrowth in established cultures. We conclude that Wnt-3a and Wnt-3 factors signal through the canonical Wnt/,-catenin pathway to regulate different aspects of SCNP development. These findings may be of therapeutic interest for the treatment of neurodegenerative diseases and nerve injury. © 2010 Wiley-Liss, Inc. [source] Low-density lipoprotein receptor-related protein (LRP)-2/megalin is transiently expressed in a subpopulation of neural progenitors in the embryonic mouse spinal cordTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 2 2005Grzegorz Wicher Abstract The lipoprotein receptor LRP2/megalin is expressed by absorptive epithelia and involved in receptor-mediated endocytosis of a wide range of ligands. Megalin is expressed in the neuroepithelium during central nervous system (CNS) development. Mice with homozygous deletions of the megalin gene show severe forebrain abnormalities. The possible role of megalin in the developing spinal cord, however, is unknown. Here we examined the spatial and temporal expression pattern of megalin in the embryonic mouse spinal cord using an antibody that specifically recognizes the cytoplasmic part of the megalin molecule. In line with published data, we show expression of megalin in ependymal cells of the central canal from embryonic day (E)11 until birth. In addition, from E11 until E15 a population of cells was found in the dorsal part of the developing spinal cord strongly immunoreactive against megalin. Double labeling showed that most of these cells express vimentin, a marker for immature astrocytes and radial glia, but not brain lipid binding protein (BLBP), a marker for radial glial cells, or glial fibrillary acidic protein (GFAP), a marker for mature astrocytes. These findings indicate that the majority of the megalin-positive cells are astroglial precursors. Megalin immunoreactivity was mainly localized in the nuclei of these cells, suggesting that the cytoplasmic part of the megalin molecule can be cleaved following ligand binding and translocated to the nucleus to act as a transcription factor or regulate other transcription factors. These findings suggest that megalin has a crucial role in the development of astrocytes of the spinal cord. J. Comp. Neurol. 492:123,131, 2005. © 2005 Wiley-Liss, Inc. [source] Early Embryonic Development of the Camel Lumbar Spinal Cord SegmentANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2005M. E. Abd Elmonem The lumbar spinal cord segment of the camel embryo at CVRL 2.4 to 28 cm was examined. Major changes are occurring in the organization of the lumbar spinal cord segments during this early developmental period. At the CVRL 2.4, 2.7 and 3.6 cm the three primary layers, ependymal cells layer, mantle cells layer, marginal cells layer in the developing lumber spinal cord segment were demonstrated. The mantle layer is the first to show striking differentiation, while the marginal layer is represented by thin outer rim. Proliferation and differentiation of the neuroepithelial cells in the developing spinal cord produce the thick lateral walls, thin roof and floor plates. The spinal ganglion and dorsal root of the spinal nerve are differentiated. At 2.7 cm CVRL differential thickening of the lateral walls produces a shallow longitudinal groove called sulcus limitans, which separates the dorsal part (alar plate) from ventral part (basal plate). The ventral root of the spinal nerve, the spinal cord and ganglion are embedded in loose mesenchyme, which tends to differentiate into spinal meninges. At 3.6 cm CVRL the basal plate, which is the future ventral gray horn, seem to be quite voluminous and the dorsal and ventral roots unite to form the beginning of the spinal nerve. At 5.5 cm CVRL the alar plates enlarge forming the dorsal septum. At 8.4 cm to 10.5 cm CVRL the basal plates enlarge, and bulge ventrally on each side of the midline producing the future ventral medium fissure, and the white and gray matters can be recognized. At 28 cm CVRL the lumen of the spinal cord is differentiated into the central canal bounded dorsally and ventrally by dorsal and ventral gray commissures, and therefore the gray matter takes the appearance of a butterfly. The lumber spinal nerve and their roots are well distinguished. [source] | ||||||||||