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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 1,261 records · Page 70Linked to original sources

bioRxiv2017

Self-assembling all-enzyme hydrogels for biocatalytic flow processes

We describe the construction of binary self-assembling all-enzyme hydrogels that are comprised entirely of two tetrameric globular enzymes, the stereoselective dehydrogenase LbADH and the cofactor-regenerating glucose 1-dehydrogenase GDH. The enzymes were genetically fused with a SpyTag or SpyCatcher domain, respectively, to generate two complementary homo-tetrameric building blocks that polymerise under physiological conditions into porous hydrogels. The biocatalytic gels were used for the highly stereoselective reduction of a prochiral diketone substrate where they showed the typical behaviour of the coupled kinetics of coenzyme regenerating reactions in the substrate channelling regime. They effectively sequestrate the NADPH cofactor even under continuous flow conditions. Owing to their sticky nature, the gels can be readily mounted in simple microfluidic reactors without the need for supportive membranes. The reactors revealed extraordinary high space-time yields with nearly quantitative conversion (>95%), excellent stereoselectivity (d.r. > 99:1), and total turnover numbers of the expensive cofactor NADP(H) that are amongst the highest values ever reported.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC=\"FIGDIR/small/240325_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (30K):\norg.highwire.dtl.DTLVardef@19a66b9org.highwire.dtl.DTLVardef@1ce1a41org.highwire.dtl.DTLVardef@1dac96org.highwire.dtl.DTLVardef@2db317_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2017

Isoxanthopterin: An Optically Functional Biogenic Crystal in the Eyes of Decapod Crustaceans

The eyes of some aquatic animals form images through reflective optics. Shrimp, lobsters, crayfish and prawns possess reflecting superposition compound eyes, composed of thousands of square-faceted eye-units (ommatidia). Mirrors in the upper part of the eye (the distal mirror) reflect light collected from many ommatidia onto the underlying photosensitive elements of the retina, the rhabdoms. A second reflector, the tapetum, underlying the retina, back-scatters dispersed light onto the rhabdoms. Using microCT and cryo-SEM imaging accompanied by in situ micro-X-ray diffraction and micro-Raman spectroscopy, we investigated the hierarchical organization and materials properties of the reflective systems at high resolution and under close to physiological conditions. We show that the distal mirror consists of three or four layers of sparse plate-like nano-crystals. The tapetum is a diffuse reflector composed of hollow nanoparticles constructed from concentric lamellae of crystals. Isoxanthopterin, a pteridine analog of guanine, forms both the reflectors in the distal mirror and in the tapetum. The crystal structure of isoxanthopterin was determined from crystal structure prediction calculations and verified by comparison with experimental X-ray diffraction. The extended hydrogen bonded layers of the molecules results in an extremely high calculated refractive index in the H-bonded plane, n = 1.96, which makes isoxanthopterin crystals an ideal reflecting material. The crystal structure of isoxanthopterin, together with a detailed knowledge of the reflector superstructures, provide a rationalization of the reflective optics of the crustacean eye.\n\nSignificanceAquatic animals use reflectors in their eyes either to form images or to increase photon capture. Guanine is the most widespread molecular component of these reflectors. Here we show that crystals of isoxanthopterin, a pteridine analogue of guanine, form both the image-forming distal mirror and the intensity-enhancing tapetum reflector in the compound eyes of some decapod crustaceans. The crystal structure of isoxanthopterin was determined, providing an explanation for why these crystals are so well suited for efficient reflection. Pteridines were previously known only as pigments and our discovery raises the question of which other organic molecules may be used to form crystals with superior reflective properties either in organisms or in artificial optical devices.

bioengineering↗

bioRxiv2017

An ordered pattern of Ana2 phosphorylation by Plk4 is required for centriole assembly

Polo-like kinase 4 (Plk4) initiates an early step in centriole assembly by phosphorylating Ana2/STIL, a structural component of the procentriole. Here, we show that Plk4 binding to the central coiled-coil (CC) of Ana2 is a conserved event, involving Polo-box 3 and a previously unidentified putative CC located adjacent to the kinase domain. Ana2 binding stimulates Plk4 kinase activity in vitro, and, in turn, is phosphorylated along its length. Previous studies showed that Plk4 phosphorylates the C-terminal STAN domain of Ana2/STIL, triggering binding and recruitment of the cartwheel protein Sas6 to the procentriole assembly site. However, the physiological relevance of N-terminal phosphorylation was unknown. We found that Plk4 first phosphorylates the extreme N-terminus of Ana2 which is critical for subsequent STAN domain modification. Phosphorylation of the central region then breaks the Plk4-Ana2 interaction. This phosphorylation pattern is important for centriole assembly and integrity because replacement of endogenous Ana2 with phospho-Ana2 mutants disrupts distinct steps in Ana2 function and inhibits centriole duplication.

cell biology↗

bioRxiv2017

Decoding the gene co-expression network underlying the ability of Gevuina avellana Mol. to live in diverse light conditions

O_LIGevuina avellana Mol. (Proteaceae) is a typical tree from the South American temperate rainforest. Although this species mostly regenerates in shaded understories, it exhibits an exceptional ecological breadth, being able to live under a wide range of light conditions. Here we studied the genetic basis regulating physiological acclimation of the photosynthetic responses of G. avellana under contrasting light conditions.\nC_LIO_LIWe analyzed carbon assimilation and light energy used for photochemical process in plants acclimated to contrasting light conditions. Also, we used a transcriptional profile of leaf primordia from G. avellana saplings growing under different light environments to identify the gene co-expression network underpinning photosynthetic performance and light-related processes.\nC_LIO_LIThe photosynthetic parameters revealed optimal performance regardless of light conditions. Strikingly, the mechanism involved in dissipation of excess light energy showed no significant differences between high and low-light acclimated plants. The gene co-expression network defined a community structure consistent with the photochemical responses, including genes involved mainly in assembly and functioning of photosystems, photoprotection, and retrograde signaling.\nC_LIO_LIOur ecophysiological genomics approach provides an understanding of the molecular regulatory mechanisms that allows this tree to have an optimal balance between photochemical, photoprotective and antioxidant performance in the diverse light habitats it encounters in nature.\nC_LI

plant biology↗

bioRxiv2017

Binocular System with Asymmetric Eyes

I elaborate binocular geometry with a novel eye model that incorporates the foveas temporalward displacement and the cornea and the lens misalignment. The formulated binocular correspondence results in longitudinal horopters that are conic sections resembling empirical horopters. When the eye models asymmetry parameters range is that which is observed in healthy eyes, abathic distance also falls within its experimentally observed range. This range in abathic distance is similar to that of the vergence resting position distance. Further, the conics orientation is specified by the eyes version angle, integrating binocular geometry with eye movement. This integration presents the possibility for modeling 3D perceptual stability during physiological eye movements.\n\nOCIS codes: (330.1400) Vision - binocular and stereopsis; (330.4060) Vision modeling

neuroscience↗

bioRxiv2017

Converting a broad matrix metalloproteinase family inhibitor into a specific inhibitor of MMP-9 and MMP-14

MMP-14 and MMP-9 are two well established cancer targets for which no specific clinically relevant inhibitor is available. Using a powerful combination of computational design and yeast surface display technology, we engineered such an inhibitor starting from a non-specific MMP inhibitor, N-TIMP2. The engineered purified N-TIMP2 variants showed enhanced specificity towards MMP-14 and MMP-9 relative to a panel of off-target MMPs. MMP-specific N-TIMP2 sequence signatures were obtained that could be understood from the structural perspective of MMP/N-TIMP2 interactions. Our MMP-9 inhibitor exhibited 1000-fold preference for MMP-9 vs. MMP-14, which is likely to translate into significant differences under physiological conditions. Our results provide new insights regarding evolution of promiscuous proteins and optimization strategies for design of inhibitors with single-target specificities.

biophysics↗

bioRxiv2017

Multivariate analysis reveals environmental and genetic determinants of element covariation in the maize grain ionome

Plants obtain elements from the soil through genetic and biochemical pathways responsive to physiological state and environment. Most perturbations affect multiple elements which leads the ionome, the full complement of mineral nutrients in an organism, to vary as an integrated network rather than a set of distinct single elements. To examine the genetic basis of covariation in the accumulation of multiple elements, we analyzed maize kernel ionomes from Intermated B73 x Mo17 (IBM) recombinant inbred populations grown in 10 environments. We compared quantitative trait loci (QTL) determining single-element variation to QTL that predict variation in principal components (PCs) of multiple-element covariance. Single-element and multivariate approaches detected partially overlapping sets of loci. In addition to loci co-localizing with single-element QTL, multivariate traits within environments were controlled by loci with significant multi-element effects not detectable using single-element traits. Gene-by-environment interactions underlying multiple-element covariance were identified through QTL analyses of principal component models of ionome variation. In addition to interactive effects, growth environment had a profound effect on the elemental profiles and multi-element phenotypes were significantly correlated with specific environmental variables.\n\nAuthor SummaryA multivariate approach to the analysis of element accumulation in the maize kernel shows that elements are not regulated independently. By describing relationships between element accumulation we identified new genetic loci invisible to single-element approaches. The mathematical combinations of elements distinguish groups of plants based on environment, demonstrating that observed variation derives from interactions between genetically controlled factors and environmental variables. These results suggest that successful application of ionomics to improve human nutrition and plant productivity requires simultaneous consideration of multiple-element effects and variation of such effects in response to environment.

plant biology↗

bioRxiv2017

A deep convolutional neural network approach for astrocyte detection

Astrocytes are involved in brain pathologies such as trauma or stroke, neurodegenerative disorders like Alzheimers and Parkinsons disease, chronic pain, and many others. Determining cell density and timing of morphological and biochemical changes is important for a proper understanding of the role of astrocytes in physiological and pathological conditions. One of the most important of such analyses is astrocytes count within a complex tissue environment in microscopy images. The most widely used approaches for the quantification of microscopy images data are either manual stereological cell counting or semi-automatic segmentation techniques. Detecting astrocytes automatically is a highly challenging computational task, for which we currently lack efficient image analysis tools. In this study, we developed a fast and fully automated software that assesses the number of astrocytes using Deep Convolutional Neural Networks (DCNN). The method highly outperforms state-of-the-art image analysis and machine learning methods and provides detection accuracy and precision comparable to that of human experts. Additionally, the runtime of cell detection is significantly less than other three analyzed computational methods, and it is faster than human observers by orders of magnitude. We applied DCNN-based method to examine the number of astrocytes in different brain regions of rats with opioid-induced hyperalgesia/tolerance (OIH/OIT) as morphine tolerance is believed to activate glial cells in the brain. We observed strong positive correlation between manual cell detection and DCNN-based analysis method for counting astrocytes in the brains of experimental animals.

bioinformatics↗

bioRxiv2018

meaRtools: an R package for the Comprehensive Analysis of Neuronal Networks Recorded on Multi-Electrode Arrays

Here we present an open-source R package meaRtools that provides a platform for analyzing neuronal networks recorded on Microelectrode Arrays (MEAs). Cultured neuronal networks monitored with MEAs are now being widely used to characterize in vitro models of neurological disorders and to evaluate pharmaceutical compounds. meaRtools provides core algorithms for MEA spike train analysis, feature extraction, statistical analysis and plotting of multiple MEA recordings with multiple genotypes and treatments. meaRtools functionality covers novel solutions for spike train analysis, including algorithms to assess electrode cross-correlation using the spike train tiling coefficient (STTC), mutual information, synchronized bursts and entropy within cultured wells. Also integrated is a solution to account for bursts variability originating from mixed-cell neuronal cultures. The package provides a statistical platform built specifically for MEA data that can combine multiple MEA recordings and compare extracted features between different genetic models or treatments. We demonstrate the utilization of meaRtools to successfully identify epilepsy-like phenotypes in neuronal networks from Celf4 knockout mice. The package is freely available under the GPL license (GPL>=3) and is updated frequently on the CRAN web-server repository. The package, along with full documentation can be downloaded from: https://cran.r-project.org/web/packages/meaRtools/.\n\nAuthor summaryCultured neuronal networks are widely used to study and characterize neuronal network activity. Among the many uses of neuronal cultures are the capabilities to evaluate neurotoxicity and the effects of pharmacological compounds on cellular physiology. Multi-well microelectrode arrays (MEAs) can collect high-throughput data from multiple neuronal cultures simultaneously, and thereby make possible hypotheses-driven inquiries into neurobiology and neuropharmacology. The analysis of MEA-derived information presents many computational challenges. High frequency data recorded simultaneously from hundreds of electrodes can be difficult to handle. The need to compare network activity across various drug treatments or genotypes recorded on the same plate from experiments lasting several weeks presents another challenge. These challenges inspired us to develop meaRtools; an MEA data analysis package that contains new methods to characterize network activity patterns, which are illustrated here using examples from a genetic mouse model of epilepsy. Among the highlights of meaRtools are novel algorithms designed to characterize neuronal activity dynamics and network properties such as bursting and synchronization, options to combine multiple recordings and use a robust statistical framework to draw appropriate statistical inferences, and finally data visualizations and plots. In summary, meaRtools provides a platform for the analyses of singular and longitudinal MEA experiments.

neuroscience↗

bioRxiv2018

A Multi-layer, Self-aligning Hydrogel Micro-molding Process Offering a Fabrication Route to Perfusable 3D In-Vitro Microvasculature

The in-vitro fabrication of hierarchical biological systems such as human vasculature, which are made up of two or more cell types with intricate co-culture architectures, is by far one of the most complicated challenges that tissue engineers have faced. Here, we introduce a versatile method to create multi-layered, cell-laden hydrogel microstructures with coaxial geometries and heterogeneous mechanical and biological properties. The technique can be used to build in-vitro vascular networks that are fully embedded in hydrogels of physiologically realistic mechanical stiffness. Our technique produces free-standing 3D structures, eliminating rigid polymeric surfaces from the vicinity of cells and allowing layers of multiple cell types to be defined with tailored extracellular matrix (ECM) composition and stiffness, and in direct contact with each other. We demonstrate co-axial geometries with diameters ranging from 200-2000 m and layer thicknesses as small as 50-200 {micro}m in agarose- collagen (AC) composite hydrogels. Coaxial geometries with such fine feature sizes are beyond the capabilities of most bioprinting techniques. A potential application of such a structure is to simulate vascular networks in the brain with endothelial cells surrounded by multiple layers of pericytes and other glial cells. For this purpose, the composition and mechanical properties of the composite AC hydrogels have been optimized for cell viability and biological performance of endothelial and glial cell types in both 2D and 3D culture modes. Multi-layered vascular constructs with an endothelial layer surrounded by layers of glial cells have been fabricated. This prototype in-vitro model resembles vascular geometries and opens the way for complex multi-luminal blood vessels to be fabricated.

bioengineering↗

bioRxiv2018

The genome of the water strider Gerris buenoi reveals expansions of gene repertoires associated with adaptations to life on the water

The semi-aquatic bugs conquered water surfaces worldwide and occupy ponds, streams, lakes, mangroves, and even open oceans. As such, they inspired a range of scientific studies from ecology and evolution to developmental genetics and hydrodynamics of fluid locomotion. However, the lack of a representative water strider genome hinders thorough investigations of the mechanisms underlying the processes of adaptation and diversification in this group. Here we report the sequencing and manual annotation of the Gerris buenoi (G. buenoi) genome, the first water strider genome to be sequenced so far. G. buenoi genome is about 1 000Mb and the sequencing effort recovered 20 949 predicted protein-coding genes. Manual annotation uncovered a number of local (tandem and proximal) gene duplications and expansions of gene families known for their importance in a variety of processes associated with morphological and physiological adaptations to water surface lifestyle. These expansions affect key processes such as growth, vision, desiccation resistance, detoxification, olfaction and epigenetic components. Strikingly, the G. buenoi genome contains three Insulin Receptors, a unique case among metazoans, suggesting key changes in the rewiring and function of the insulin pathway. Other genomic changes include wavelength sensitivity shifts in opsin proteins likely in association with the requirements of vision in water habitats. Our findings suggest that local gene duplications might have had an important role during the evolution of water striders. These findings along with the G. buenoi genome open exciting research opportunities to understand adaptation and genome evolution of this unique hemimetabolous insect.

genomics↗

bioRxiv2018

Root Responses to Heterogeneous Nitrate Availability are Mediated by trans-Zeatin in Arabidopsis Shoots

Plants are subjected to variable nitrogen (N) availability including frequent spatial nitrate (NO3-) heterogeneity in soil. Thus, plants constantly adapt their genome expression and root physiology in order to optimize N acquisition from this heterogeneous source. These adaptations rely on a complex and long-distance root-shoot-root signaling network that is still largely unknown. Here, we used a combination of reverse genetics, transcriptomic analysis, NO3- uptake experiments and hormone profiling under conditions of homogeneous or heterogeneous NO3- availability to characterize the systemic signaling involved. We demonstrate the important role of the trans-zeatin form of cytokinin (CK) in shoots, in particular using a mutant altered for ABCG14-mediated trans-zeatin-translocation from the root to the shoot, in mediating: (i) rapid long distance N-demand signaling and (ii) long term functional adaptations to heterogeneous NO3- supply, including changes in NO3- transport capacity and root growth modifications. We also provide insights into the potential CK-dependent and independent shoot-to-root signals involved in root adaptation to heterogeneous N availability.

plant biology↗

bioRxiv2018

Sleep-like bistability, loss of causality and complexity in the brain of Unresponsive Wakefulness Syndrome patients

Unresponsiveness Wakefulness Syndrome (UWS) patients may retain intact portions of the thalamocortical system that are spontaneously active and responsive to sensory stimuli. In these patients, Transcranial Magnetic Stimulation combined with electroencephalography (TMS/EEG) also reveals preserved cortical reactivity, but in most cases, the residual thalamocortical circuits fail to engage complex causal interactions, as assessed by the perturbational complexity index (PCI). Another condition during which thalamocortical circuits are intact, active and reactive, yet unable to generate complex responses, is physiological non-rapid eye movement (NREM) sleep. The underlying mechanism is bistability: the tendency of cortical neurons to fall into a silent period (OFF-period) upon receiving an input. Here we tested whether a pathological form of bistability may be responsible for loss of brain complexity in UWS patients. Time-frequency decomposition analysis of TMS/EEG responses in UWS patients revealed the occurrence of OFF-periods (detected as a transient suppression of high-frequency oscillations in the EEG) similar to the ones evoked by TMS in the cortex of healthy sleeping subjects. Pathological OFF-periods were detected in any cortical area, significantly impaired local causal interactions (as measured by PLF) and prevented the build-up of global complexity (as measured by PCI) in the brain of UWS patients. Our results draw a first link between neuronal events (OFF-periods) and global brain dynamics (complexity) in UWS patients. To the extent that sleep-like bistability represents the common functional endpoint of loss of complexity, detecting its presence and tracking its evolution over time, may offer a valuable read-out to devise, guide and titrate therapeutic strategies aimed at restoring consciousness.

neuroscience↗

bioRxiv2018

An Automated Workflow for Segmenting Single Adult Cardiac Cells from Large-Volume Serial Block-Face Scanning Electron Microscopy Data

This paper presents a new algorithm to automatically segment the myofibrils, mitochondria and nuclei within single adult cardiac cells that are part of a large serial-block-face scanning electron microscopy (SBF-SEM) dataset. The algorithm only requires a set of manually drawn contours that roughly demarcate the cell boundary at routine slice intervals (every 50th, for example). The algorithm correctly classified pixels within the single cell with 97% accuracy when compared to manual segmentations. One entire cell and the partial volumes of two cells were segmented. Analysis of segmentations within these cells showed that myofibrils and mitochondria occupied 47.5% and 51.6% on average respectively, while the nuclei occupy 0.7% of the cell for which the entire volume was captured in the SBF-SEM dataset. Mitochondria clustering increased at the periphery of the nucleus region and branching points of the cardiac cell. The segmentations also showed high area fraction of mitochondria (up to 70% of the 2D image slice) in the sub-sarcolemmal region, whilst it was closer to 50% in the intermyofibrillar space. We finally demonstrate that our segmentations can be turned into 3D finite element meshes for cardiac cell computational physiology studies. We offer our large dataset and MATLAB implementation of the algorithm for research use at www.github.com/CellSMB/sbfsem-cardiac-cell-segmenter/. We anticipate that this timely tool will be of use to cardiac computational and experimental physiologists alike who study cardiac ultrastructure and its role in heart function.

bioengineering↗

bioRxiv2018

The Homeostatic Logic of Reward

Energy homeostasis depends on behavior to predictively regulate metabolic states within narrow bounds. Here we review three theories of homeostatic control and ask how they provide insight into the circuitry underlying energy homeostasis. We offer two contributions. First, we detail how control theory and reinforcement learning are applied to homeostatic control. We show how these schemes rest on implausible assumptions; either via circular definitions, unprincipled drive functions, or by ignoring environmental volatility. We argue active inference can elude these shortcomings while retaining important features of each model. Second, we review the neural basis of energetic control. We focus on a subset of arcuate subpopulations that project directly to, and are thus in a privileged position to opponently modulate, dopaminergic cells as a function of energetic predictions over a spectrum of time horizons. We discuss how this can be interpreted under these theories, and how this can resolve paradoxes that have arisen. We propose this circuit constitutes a homeostatic-reward interface that underwrites the conjoint optimisation of physiological and behavioural homeostasis.

neuroscience↗

bioRxiv2018

Reward signalling in brainstem nuclei under glycemic flux

Phasic dopamine release from mid-brain dopaminergic neurons signals errors of reward prediction (RPE). If reward maximisation is to maintain homeostasis, then the value of primary rewards should be coupled to the homeostatic errors they remediate. This leads to the prediction that RPE signals should be configured as a function of homeostatic state and thus, diminish with the attenuation of homeostatic error. To test this hypothesis, we collected a large volume of functional MRI data from five human volunteers on four separate days. After fasting for 12 hours, subjects consumed preloads that differed in glucose concentration. Participants then underwent a Pavlovian cue-conditioning paradigm in which the colour of a fixation-cross was stochastically associated with the delivery of water or glucose via a gustometer. This design afforded computation of RPE separately for better- and worse-than expected outcomes during ascending and descending trajectories of physiological serum glucose fluctuations. In the parabrachial nuclei, variations in regional activity coding positive RPEs scaled positively with serum glucose for ascending and descending glucose levels. The ventral tegmental area and substantia nigra became more sensitive to negative RPEs when glucose levels were ascending. Together, the results show that RPE signals in key brainstem structures are modulated by homeostatic trajectories of naturally occurring glycemic flux, revealing a tight interplay between homeostatic state and the neural encoding of primary reward in the human brain.

neuroscience↗

bioRxiv2018

Phenotypic convergence in the brain: distinct transcription factors regulate common terminal neuronal characters

Transcription factors regulate the molecular, morphological, and physiological characters of neurons and generate their impressive cell type diversity. To gain insight into general principles that govern how transcription factors regulate cell type diversity, we used large-scale single-cell mRNA sequencing to characterize the extensive cellular diversity in the Drosophila optic lobes. We sequenced 55,000 single optic lobe neurons and glia and assigned them to 52 clusters of transcriptionally distinct single cells. We validated the clustering and annotated many of the clusters using RNA sequencing of characterized FACS-sorted single cell types, as well as marker genes specific to given clusters. To identify transcription factors responsible for inducing specific terminal differentiation features, we used machine-learning to generate a random forest model. The predictive power of the model was confirmed by showing that two transcription factors expressed specifically in cholinergic (apterous) and glutamatergic (traffic-jam) neurons are necessary for the expression of ChAT and VGlut in many, but not all, cholinergic or glutamatergic neurons, respectively. We used a transcriptome-wide approach to show that the same terminal characters, including but not restricted to neurotransmitter identity, can be regulated by different transcription factors in different cell types, arguing for extensive phenotypic convergence. Our data provide a deep understanding of the developmental and functional specification of a complex brain structure.

developmental biology↗

bioRxiv2018

GSK3 Controls Migration of the Neural Crest Lineage

Migration of the neural crest lineage is critical to its physiological function. Mechanisms controlling neural crest migration are comparatively unknown, due to difficulties accessing this cell population in vivo. Here, we uncover novel requirements of glycogen synthase kinase 3 (GSK3) in regulating the neural crest. We demonstrate that GSK3 is tyrosine phosphorylated (pY) in neural crest cells and that this activation depends on anaplastic lymphoma kinase (ALK), a protein associated with neuroblastoma. Consistent with this, neuroblastoma cells with pathologically increased ALK activity express high levels of pY-GSK3 and migration of these cells can be inhibited by GSK3 or ALK blockade. In normal neural crest cells, loss of GSK3 leads to increased pFAK and misregulation of Rac1 and lamellipodin, key regulators of cell migration. Genetic reduction of GSK-3 results in failure of migration. All together, this work identifies a role for GSK3 in cell migration during neural crest development and cancer.

developmental biology↗