During patterning of the peripheral nervous system, motor axons grow sequentially out of the neural tube in a segmented fashion to ensure functional integration of the motor roots between the surrounding cartilage and bones of the developing vertebrae. This segmented outgrowth is regulated by the intrinsic properties of each segment (somite) adjacent to the neural tube, and in particular by chemical repulsive guidance cues expressed in the posterior half. Yet, knockout models for such repulsive cues still display initial segmentation of outgrowing motor axons, suggesting the existence of additional, yet unknown regulatory mechanisms of axon growth segmentation.
View Article and Find Full Text PDFThe mammalian brain contains few niches for neural stem cells (NSCs) capable of generating new neurons, whereas other regions are primarily gliogenic. Here we leverage the spatial separation of the sub-ependymal zone NSC niche and the olfactory bulb, the region to which newly generated neurons from the sub-ependymal zone migrate and integrate, and present a comprehensive proteomic characterization of these regions in comparison to the cerebral cortex, which is not conducive to neurogenesis and integration of new neurons. We find differing compositions of regulatory extracellular matrix (ECM) components in the neurogenic niche.
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View Article and Find Full Text PDFAgeing causes a decline in tissue regeneration owing to a loss of function of adult stem cell and progenitor cell populations. One example is the deterioration of the regenerative capacity of the widespread and abundant population of central nervous system (CNS) multipotent stem cells known as oligodendrocyte progenitor cells (OPCs). A relatively overlooked potential source of this loss of function is the stem cell 'niche'-a set of cell-extrinsic cues that include chemical and mechanical signals.
View Article and Find Full Text PDFDuring nervous system development, neurons extend axons along well-defined pathways. The current understanding of axon pathfinding is based mainly on chemical signaling. However, growing neurons interact not only chemically but also mechanically with their environment.
View Article and Find Full Text PDFDuring development, normal functioning, as well as in certain pathological conditions, cells are influenced not only by biochemical but also by mechanical signals. Over the past two decades, atomic force microscopy (AFM) has become one of the key tools to investigate the mechanical properties and interactions of biological samples. AFM studies have provided important insights into the role of mechanical signaling in different biological processes.
View Article and Find Full Text PDFIn this work, we incorporate and image individual fluorescent nanodiamonds in the powerful genetic model system Drosophila melanogaster. Fluorescence correlation spectroscopy and wide-field imaging techniques are applied to individual fluorescent nanodiamonds in blastoderm cells during stage 5 of development, up to a depth of 40 µm. The majority of nanodiamonds in the blastoderm cells during cellularization exhibit free diffusion with an average diffusion coefficient of (6 ± 3) × 10(-3) µm(2)/s, (mean ± SD).
View Article and Find Full Text PDFThe ZIC transcription factors are key mediators of embryonic development and ZIC3 is the gene most commonly associated with situs defects (heterotaxy) in humans. Half of patient ZIC3 mutations introduce a premature termination codon (PTC). In vivo, PTC-containing transcripts might be targeted for nonsense-mediated decay (NMD).
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