Computational cannula microscopy (CCM) is a high-resolution widefield fluorescence imaging approach deep inside tissue, which is minimally invasive. Rather than using conventional lenses, a surgical cannula acts as a lightpipe for both excitation and fluorescence emission, where computational methods are used for image visualization. Here, we enhance CCM with artificial neural networks to enable 3D imaging of cultured neurons and fluorescent beads, the latter inside a volumetric phantom.
View Article and Find Full Text PDFmutations cause an autosomal recessive connective tissue disorder, geleophysic dysplasia 1 (GPHYSD1), which is characterized by short stature, small hands and feet, and cardiac defects. ADAMTSL2 is a matricellular protein previously shown to interact with latent transforming growth factor-β binding protein 1 and influence assembly of fibrillin 1 microfibrils. ADAMTSL2 contains seven thrombospondin type-1 repeats (TSRs), six of which contain the consensus sequence for -fucosylation by protein fucosyltransferase 2 (POFUT2).
View Article and Find Full Text PDFComputational cannula microscopy is a minimally invasive imaging technique that can enable high-resolution imaging deep inside tissue. Here, we apply artificial neural networks to enable real-time, power-efficient image reconstructions that are more efficiently scalable to larger fields of view. Specifically, we demonstrate widefield fluorescence microscopy of cultured neurons and fluorescent beads with a field of view of 200 µm (diameter) and a resolution of less than 10 µm using a cannula of diameter of only 220 µm.
View Article and Find Full Text PDFBackground: Developmental processes, including neuronal differentiation, require precise regulation of transcription. The RE-1 silencing transcription factor (Rest), is often called a "master neuronal regulator" due to its large number of neural-specific targets. Rest recruits CoRest (Rcor) and Sin3 corepressor complexes to gene regulatory sequences.
View Article and Find Full Text PDFThe neuronal gene Arc is essential for long-lasting information storage in the mammalian brain, mediates various forms of synaptic plasticity, and has been implicated in neurodevelopmental disorders. However, little is known about Arc's molecular function and evolutionary origins. Here, we show that Arc self-assembles into virus-like capsids that encapsulate RNA.
View Article and Find Full Text PDFThe molecular basis for the decline in experience-dependent neural plasticity over age remains poorly understood. In visual cortex, the robust plasticity induced in juvenile mice by brief monocular deprivation during the critical period is abrogated by genetic deletion of Arc, an activity-dependent regulator of excitatory synaptic modification. Here, we report that augmenting Arc expression in adult mice prolongs juvenile-like plasticity in visual cortex, as assessed by recordings of ocular dominance (OD) plasticity in vivo.
View Article and Find Full Text PDFThe vertebrate hypothalamus contains persistent radial glia that have been proposed to function as neural progenitors. In zebrafish, a high level of postembryonic hypothalamic neurogenesis has been observed, but the role of radial glia in generating these new neurons is unclear. We have used inducible Cre-mediated lineage labeling to show that a population of hypothalamic radial glia undergoes self-renewal and generates multiple neuronal subtypes at larval stages.
View Article and Find Full Text PDFThe Low-density lipoprotein receptor-Related Protein (LRP) family members are essential for diverse processes ranging from the regulation of gastrulation to the modulation of lipid homeostasis. Receptors in this family bind and internalize a diverse array of ligands in the extracellular matrix (ECM). As a consequence, LRPs regulate a wide variety of cellular functions including, but not limited to lipid metabolism, membrane composition, cell motility, and cell signaling.
View Article and Find Full Text PDFBackground: Regulation of developmental signaling pathways is essential for embryogenesis. The small putative zinc finger protein, Churchill (ChCh) has been implicated in modulation of both TGF-β and FGF signaling.
Results: We used zinc finger nuclease (ZFN) mediated gene targeting to disrupt the zebrafish chch locus and generate the first chch mutations.
The transcriptional repressor Rest (Nrsf) recruits chromatin-modifying complexes to RE1 'silencer elements', which are associated with hundreds of neural genes. However, the requirement for Rest-mediated transcriptional regulation of embryonic development and cell fate is poorly understood. Conflicting views of the role of Rest in controlling cell fate have emerged from recent studies.
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