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  • Protein found to control the early migration of neurons | Newswire
    are about a second member of the Astrotactin gene family called Astn2 which they now show regulates Astn1 by controlling the amount of ASTN1 receptor that is expressed on the surface of migrating neurons The experiments published last month in the Journal of Neuroscience suggest that migrating neurons attach to their glial guides via ASTN1 and that interactions with ASTN2 promote the intracellular trafficking of ASTN1 effectively removing it from the cell surface and allowing the neuron to glide forward until a new adhesion site forms A critical new idea in the paper is that receptor trafficking of an adhesion receptor regulates movement It is very exciting to have new insights into a protein we have studied over so long a period insights that explain new aspects of how neurons migrate on glial fibers Hatten says By treating the cells with a molecule that prevents them from being able to internalize the ASTN1 receptor the researchers were able to halt the cells migration The cells were effectively stuck in place The team was then able to re initiate movement by simply washing out the molecule Imaging experiments revealed that unlike its close relative ASTN1 the adhesion protein exposed on the cell surface ASTN2 was not expressed on the cell surface but rather interacted with ASTN1 to control the amount of ASTN1 protein on the neurons surface that is available for binding to glial fibers While Astn1 has not been directly implicated in developmental disorders a number of recent human genetic studies have associated mutations in the Astn2 gene with developmental diseases such as attention deficit disorder autism and schizophrenia Both Astn1 and Astn2 are very active early in development and continue to be expressed at low levels in adulthood Hatten believes Astn2 may be important for several different types of

    Original URL path: http://newswire.rockefeller.edu/2010/07/27/protein-found-to-control-the-early-migration-of-neurons/ (2016-02-13)
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  • astrotactin | Newswire
    and schizophrenia New research identifies a gene that works behind the scenes to control a closely related adhesion gene that helps keep young neurons on the right track More Tags astrotactin Laboratory of Developmental Neurobiology Mary E Hatten April 18 1996 Science News Gene Involved in Brain Development Identified Scientists from The Rockefeller University and the Howard Hughes Medical Institute HHMI have for the first time identified a gene involved

    Original URL path: http://newswire.rockefeller.edu/tag/astrotactin/ (2016-02-13)
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  • New imaging studies reveal mechanics of neuron migration | Newswire
    places the neurons in the right layer Hatten and former postdoctoral associate David Solecki now at St Jude Children s Research Hospital focused on the mechanism of neuronal migration in cortical regions of the brain including the cerebellum hippocampus and cerebral cortex With colleagues they developed techniques to fluorescently label the motor proteins inside the tiny neurons and watch their dynamics as the cells migrate along what Hatten calls a monorail system glial fibers toward their destinations The researchers used a spinning disk confocal microscope equipped with a CCD camera to image the migration in real time at extremely high resolution allowing them to examine the motor proteins in great detail The Hatten lab had already discovered in 2004 that a conserved polarity protein par6α controls the migration of neurons along glial guides The new research published July 16 in Neuron identifies the motors regulated by par6α The researchers found that par6α localizes in a key organelle called the centrosome directly in front of the cell nucleus and effects the phosphorylation of an enzyme called the myosin light chain kinase needed to activate actomyosin motors These motors appear to pull the cell forward in discrete steps They first assemble in front of the nucleus pull the cell forward disperse as the cell pauses and then assemble again as the neuron takes another step along the glial guide The researchers demonstrated that any significant change in the dynamics of actomyosin assembly or par6α activity stops neuron migration in its tracks The mechanics of this specialized form of neuron migration seen in the developing brain are distinct from those that direct the classical migration of epithelial cells and fibroblasts as actomyosin motors in the latter are at the tip of the migrating cell in a leading edge that is relatively far removed

    Original URL path: http://newswire.rockefeller.edu/2009/07/22/new-imaging-studies-reveal-mechanics-of-neuron-migration/ (2016-02-13)
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  • Genetic profiling reveals genes active in the earliest brain circuit construction | Newswire
    found to be active at the beginning of neurogenesis specifically those involved in so called subplate neurons which form the initial scaffolding for assembling cortical circuits The genes include a substantial network related to estrogen a sex hormone whose prominence in the brain differentiates female from male That these sex pathways are involved from the get go is a particular surprise says Mary E Hatten Frederick P Rose Professor and head of the Laboratory of Developmental Neurobiology The research provides a new starting point for people to say what exactly are all of these new pathways doing The experiments conducted by former graduate student Hilleary Osheroff now at the American Museum of Natural History drew on a project developed by Hatten and Nathaniel Heintz James and Marilyn Simons Professor and head of the Laboratory of Molecular Biology called the Gene Expression Nervous System Atlas GENSAT GENSAT pioneered a genetic engineering technology that employs bacterial artificial chromosomes to visualize the contribution of thousands of genes to the mouse brain with the enhanced green fluorescent protein Osheroff screened these genes for involvement in the earliest stages of brain development when the first neurons begin to stratify across six layers that form the scaffolding of the embryonic brain inside a folding neural tube Using fluorescence activated cell sorting Osheroff isolated the neurons destined for the layer known as the subplate from the Cajal Retzius neurons which carry on beyond the subplate to the layer known as the marginal zone She identified 229 genes specifically dedicated to developing the subplate neurons and found that they were involved in a broad range of activities including cortical development cell and axon motility protein trafficking steroid hormone signaling and central nervous system degenerative diseases The work indicates the breadth of factors involved in the early development of

    Original URL path: http://newswire.rockefeller.edu/2009/05/29/genetic-profiling-reveals-genes-active-in-the-earliest-brain-circuit-construction/ (2016-02-13)
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  • New glimpse into early brain development shows how nerve cells move into position | Newswire
    in the Journal of Neuroscience by Mary E Hatten Frederick P Rose Professor and head of Rockefeller University s Laboratory of Developmental Neurobiology and Daniver Morales a postdoctoral fellow in the lab precise patterns of activity of transcription factors in the brain are responsible for defining the three major types of neurons in the cerebellum And these specific transcription factor patterns combined with the young neurons migration pathways appear to generate the cerebellum s two fundamental structures the cerebellar nuclei and the cerebellar cortex Using newly developed transcription factor pattern markers in conjunction with fluorescent microscopy Hatten and Morales found that they could visualize the three types of neurons that make up the cerebellum deep nuclei located in the very center Purkinje cells which are some of largest neurons in the brain and the tiny plentiful granule cells which make up the cerebellar granule layer From there the researchers could follow the generation and migration of these cells in the developing brain We found that cell migration pathways have exquisite timing and we see this amazing tango as different populations of cells zoom into place Hatten says One of the most notable observations that the researchers made was that their markers allowed them to image the youngest Purkinje cells ever seen and to follow the cells as they migrated into position along neural support cells called glia This was something that everyone had always assumed but had never actually been proved she says And Purkinje cells weren t the only ones to use glia for migration Neurons of the cerebellar nuclei migrate on glia too that was a real surprise Hatten and Morales found another surprise in their data one that may have implications for understanding brain cancer By watching the different transcription factor patterns they found that granule cells

    Original URL path: http://newswire.rockefeller.edu/2007/03/28/new-glimpse-into-early-brain-development-shows-how-nerve-cells-move-into-position/ (2016-02-13)
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  • Cellular Two Step | Newswire
    journey Under the microscope a migrating neuron looks like a round cell perched on a rope the glial fiber leading to its destination Rather than gliding smoothly along the fiber the neuron takes a step First it stretches out along the fiber extending what scientists call a leading process in the direction it wants to move About three minutes later the cell body catches up It s almost like a little inchworm in the way it moves says Hatten whose time lapse movies first revealed this motion in 1987 With each step the cells travel a little more than a micron or about half the width of a hair over the course of an hour The new study shows that a surprising mechanism underlies neuronal migration The Rockefeller scientists suspected that the cytoskeleton the scaffold of elements called microtubules that support a cell s three dimensional shape was important to neuron migration They knew that disrupting the cytoskeleton with chemicals prevents the cell from moving In addition problems with the cytoskeleton are implicated in human disorders in which nerve cells fail to migrate properly such as Miller Deiker syndrome But no one had previously watched the cytoskeleton in living neurons in real time The researchers took a new type of fluorescent dye called Venus which glows 20 times brighter than other dyes and tagged the microtubules of a type of mouse neuron called a granule cell Rockefeller scientist Tarun Kapoor Ph D an expert on the centrosome and on techniques for visualizing microtubules collaborated with Hatten and her lab colleagues to create images showing these structures in extraordinary detail Kapoor is head of Rockefeller s Laboratory of Chemistry and Cell Biology When the scientists looked at the cells with a spinning disk confocal microscope the dye revealed a cage like structure around the cell s nucleus Its like a bingo cage says Hatten It holds the nucleus The experiment confirmed the existence of this cage which had been controversial Although the cage is essential for the cell to migrate further experiments showed that it does not initiate cell movement Comparing the elements of the cage in migrating and stationary cells the researchers found no difference Next the researchers looked at the protein Par6 alpha referred to as mPar6 alpha in mouse cells Recent studies in other laboratories led the scientists to believe that mPar6 alpha helps give a cell polarity in a migrating cell a leading and a trailing end Because migrating neurons are highly polarized Hatten and her coworkers suspected that mPar6 alpha was active in them Again the researchers used Venus this time to label mPar6 alpha protein Its bright yellow glow concentrated in the centrosome the organelle located just in front of the nucleus in migrating cells which plays a role in organizing the cytoskeleton This in itself was an interesting discovery The centrosome has a large number of proteins that make up its structure Most other known proteins in the centrosome are structural says Hatten mPar6

    Original URL path: http://newswire.rockefeller.edu/2004/10/12/cellular-two-step/ (2016-02-13)
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  • cell migration | Newswire
    More Tags ACF7 cell migration Elaine Fuchs October 12 2004 Science News Cellular Two Step Following the often quoted advice of Yogi Berra You can observe a lot by just watching Rockefeller University scientists show that nerve cells in the developing brains of humans and other mammals move in a two part step led by a structure within the cell called the centrosome Once the centrosome the key organizing point

    Original URL path: http://newswire.rockefeller.edu/tag/cell-migration/ (2016-02-13)
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  • GenSAT (Gene Expression Nervous System Atlas) Project announced | Newswire
    searchable database of gene expression in all central nervous system cell types for individual genes What s more Gensat provides the tools BAC vectors and transgenic mice used in the project for researchers interested in following up on new disease based insights revealed in the atlas One hundred fifty genes are analyzed in the new database at www gensat org with 100 more genes scheduled for posting soon We are providing more information in our database than has ever been known in the central nervous system says Hatten professor and head of the Laboratory of Developmental Neurobiology at Rockefeller There isn t a single gene among the 150 currently on our public atlas that has been studied in the range of detail that we have provided If biologists tend to explore things locally in great detail we ve started examining a global economy of the central nervous system Gensat analyzes up to five genes per week in a high throughput laboratory space provided by The Rockefeller University Heintz and Hatten plan to analyze gene expression in all central nervous system cell types for 250 300 genes per year These two committed scientists along with their formidable research team are doing precisely what researchers should do with the information generated by the whole genome sequencing projects says Rockefeller University President Paul Nurse Their visionary efforts are expanding the possibilities for research and cures in neurobiology Landmarks in the brain Maps are valuable when they exhibit distinguishing features of the landscape The same is true for Gensat When the two Rockefeller scientists conceived the project four years ago Hatten knew she would need to put her considerable expertise in imaging the brain to work if Gensat was going to succeed Today the Gensat project recreates for scientists and students the experience of sitting down to look at brain specimens at a microscope Seeing genes expressed in every cell type in the brain and viewing that expression in a traditional anatomical format provide researchers with more insights about the function of genes To achieve this result the project s automated microscope records mouse brain specimens for every gene in the atlas at three developmental stages The images are captured at high resolution checked for accuracy by several of the 20 researchers involved with the project annotated and prepared for inclusion in the database The organizational challenge alone for such a large scale project is impressive But Heintz and Hatten faced more than an organizational challenge when they started out The means of displaying high resolution digital images on the scale they envisioned simply did not exist It was like going into a bike shop and designing a bike that no one has ever imagined before says Hatten All the components were available but we had to put them together and design the computing systems to run them for the first time The lead duo were fortunate to attract gifted scientists and a programmer to the project without whom they would never have achieved

    Original URL path: http://newswire.rockefeller.edu/2003/10/29/gensat-gene-expression-nervous-system-atlas-project-announced/ (2016-02-13)
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