Filter
Associated Lab
- Aguilera Castrejon Lab (2) Apply Aguilera Castrejon Lab filter
- Ahrens Lab (5) Apply Ahrens Lab filter
- Aso Lab (3) Apply Aso Lab filter
- Betzig Lab (7) Apply Betzig Lab filter
- Beyene Lab (1) Apply Beyene Lab filter
- Bock Lab (5) Apply Bock Lab filter
- Branson Lab (3) Apply Branson Lab filter
- Card Lab (2) Apply Card Lab filter
- Cardona Lab (4) Apply Cardona Lab filter
- Clapham Lab (2) Apply Clapham Lab filter
- Darshan Lab (2) Apply Darshan Lab filter
- Dickson Lab (5) Apply Dickson Lab filter
- Druckmann Lab (3) Apply Druckmann Lab filter
- Dudman Lab (4) Apply Dudman Lab filter
- Espinosa Medina Lab (3) Apply Espinosa Medina Lab filter
- Feliciano Lab (1) Apply Feliciano Lab filter
- Fitzgerald Lab (2) Apply Fitzgerald Lab filter
- Funke Lab (1) Apply Funke Lab filter
- Gonen Lab (2) Apply Gonen Lab filter
- Grigorieff Lab (4) Apply Grigorieff Lab filter
- Harris Lab (4) Apply Harris Lab filter
- Heberlein Lab (2) Apply Heberlein Lab filter
- Hermundstad Lab (1) Apply Hermundstad Lab filter
- Hess Lab (5) Apply Hess Lab filter
- Jayaraman Lab (4) Apply Jayaraman Lab filter
- Ji Lab (1) Apply Ji Lab filter
- Johnson Lab (1) Apply Johnson Lab filter
- Keleman Lab (2) Apply Keleman Lab filter
- Keller Lab (6) Apply Keller Lab filter
- Koay Lab (5) Apply Koay Lab filter
- Lavis Lab (6) Apply Lavis Lab filter
- Lee (Albert) Lab (1) Apply Lee (Albert) Lab filter
- Li Lab (2) Apply Li Lab filter
- Lippincott-Schwartz Lab (12) Apply Lippincott-Schwartz Lab filter
- Liu (Zhe) Lab (7) Apply Liu (Zhe) Lab filter
- Looger Lab (15) Apply Looger Lab filter
- O'Shea Lab (1) Apply O'Shea Lab filter
- Pachitariu Lab (4) Apply Pachitariu Lab filter
- Pavlopoulos Lab (1) Apply Pavlopoulos Lab filter
- Pedram Lab (3) Apply Pedram Lab filter
- Podgorski Lab (4) Apply Podgorski Lab filter
- Reiser Lab (2) Apply Reiser Lab filter
- Romani Lab (3) Apply Romani Lab filter
- Rubin Lab (6) Apply Rubin Lab filter
- Saalfeld Lab (3) Apply Saalfeld Lab filter
- Satou Lab (1) Apply Satou Lab filter
- Scheffer Lab (2) Apply Scheffer Lab filter
- Schreiter Lab (4) Apply Schreiter Lab filter
- Simpson Lab (1) Apply Simpson Lab filter
- Singer Lab (4) Apply Singer Lab filter
- Spruston Lab (6) Apply Spruston Lab filter
- Stern Lab (5) Apply Stern Lab filter
- Sternson Lab (2) Apply Sternson Lab filter
- Stringer Lab (4) Apply Stringer Lab filter
- Svoboda Lab (14) Apply Svoboda Lab filter
- Tebo Lab (2) Apply Tebo Lab filter
- Tillberg Lab (2) Apply Tillberg Lab filter
- Truman Lab (4) Apply Truman Lab filter
- Turaga Lab (2) Apply Turaga Lab filter
- Turner Lab (2) Apply Turner Lab filter
- Wang (Shaohe) Lab (4) Apply Wang (Shaohe) Lab filter
- Zlatic Lab (1) Apply Zlatic Lab filter
Associated Project Team
Publication Date
- December 2019 (9) Apply December 2019 filter
- November 2019 (12) Apply November 2019 filter
- October 2019 (20) Apply October 2019 filter
- September 2019 (15) Apply September 2019 filter
- August 2019 (15) Apply August 2019 filter
- July 2019 (14) Apply July 2019 filter
- June 2019 (22) Apply June 2019 filter
- May 2019 (13) Apply May 2019 filter
- April 2019 (18) Apply April 2019 filter
- March 2019 (20) Apply March 2019 filter
- February 2019 (20) Apply February 2019 filter
- January 2019 (21) Apply January 2019 filter
- Remove 2019 filter 2019
Type of Publication
199 Publications
Showing 101-110 of 199 resultsEach faculty recruiting season, many postdocs ask, "What is a chalk talk?" The chalk talk is many things-a sales pitch, a teaching demonstration, a barrage of questions, and a description of a future research program. The chalk talk is arguably the most important component of a faculty search interview. Yet few postdocs or grad students receive training or practice in giving a chalk talk. In the following essay, I'll cover the basics of chalk talk design and preparation.
Oriented cell divisions are controlled by a conserved molecular cascade involving Gαi, LGN, and NuMA. Here, we show that NDP52 regulates spindle orientation via remodeling the polar cortical actin cytoskeleton. siRNA-mediated NDP52 suppression surprisingly revealed a ring-like compact subcortical F-actin architecture surrounding the spindle in prophase/prometaphase cells, which resulted in severe defects of astral microtubule growth and an aberrant spindle orientation. Remarkably, NDP52 recruited the actin assembly factor N-WASP and regulated the dynamics of the subcortical F-actin ring in mitotic cells. Mechanistically, NDP52 was found to bind to phosphatidic acid-containing vesicles, which absorbed cytoplasmic N-WASP to regulate local filamentous actin growth at the polar cortex. Our TIRFM analyses revealed that NDP52-containing vesicles anchored N-WASP and shortened the length of actin filaments in vitro. Based on these results we propose that NDP52-containing vesicles regulate cortical actin dynamics through N-WASP to accomplish a spatiotemporal regulation between astral microtubules and the actin network for proper spindle orientation and precise chromosome segregation. In this way, intracellular vesicles cooperate with microtubules and actin filaments to regulate proper mitotic progression. Since NDP52 is absent from yeast, we reason that metazoans have evolved an elaborate spindle positioning machinery to ensure accurate chromosome segregation in mitosis.
Animal locomotion requires spatiotemporally coordinated contraction of muscles throughout the body. Here, we investigate how contractions of antagonistic groups of muscles are intersegmentally coordinated during bidirectional crawling of Drosophila larvae. We identify two pairs of higher-order premotor excitatory interneurons present in each abdominal neuromere that intersegmentally provide feedback to the adjacent neuromere during motor propagation. The two feedback neuron pairs are differentially active during either forward or backward locomotion but commonly target a group of premotor interneurons that together provide excitatory inputs to transverse muscles and inhibitory inputs to the antagonistic longitudinal muscles. Inhibition of either feedback neuron pair compromises contraction of transverse muscles in a direction-specific manner. Our results suggest that the intersegmental feedback neurons coordinate contraction of synergistic muscles by acting as delay circuits representing the phase lag between segments. The identified circuit architecture also shows how bidirectional motor networks could be economically embedded in the nervous system.
Understanding genetic and cellular bases of adult form remains a fundamental goal at the intersection of developmental and evolutionary biology. The skin pigment cells of vertebrates, derived from embryonic neural crest, are a useful system for elucidating mechanisms of fate specification, pattern formation, and how particular phenotypes impact organismal behavior and ecology. In a survey of fishes, including the zebrafish , we identified two populations of white pigment cells-leucophores-one of which arises by transdifferentiation of adult melanophores and another of which develops from a yellow-orange xanthophore or xanthophore-like progenitor. Single-cell transcriptomic, mutational, chemical, and ultrastructural analyses of zebrafish leucophores revealed cell-type-specific chemical compositions, organelle configurations, and genetic requirements. At the organismal level, we identified distinct physiological responses of leucophores during environmental background matching, and we showed that leucophore complement influences behavior. Together, our studies reveal independently arisen pigment cell types and mechanisms of fate acquisition in zebrafish and illustrate how concerted analyses across hierarchical levels can provide insights into phenotypes and their evolution.
Summary This review describes how direct visualization of the dynamic interactions of cells with different extracellular matrix microenvironments can provide novel insights into complex biological processes. Recent studies have moved characterization of cell migration and invasion from classical 2D culture systems into 1D and 3D model systems, revealing multiple differences in mechanisms of cell adhesion, migration and signalling—even though cells in 3D can still display prominent focal adhesions. Myosin II restrains cell migration speed in 2D culture but is often essential for effective 3D migration. 3D cell migration modes can switch between lamellipodial, lobopodial and/or amoeboid depending on the local matrix environment. For example, “nuclear piston” migration can be switched off by local proteolysis, and proteolytic invadopodia can be induced by a high density of fibrillar matrix. Particularly, complex remodelling of both extracellular matrix and tissues occurs during morphogenesis. Extracellular matrix supports self-assembly of embryonic tissues, but it must also be locally actively remodelled. For example, surprisingly focal remodelling of the basement membrane occurs during branching morphogenesis—numerous tiny perforations generated by proteolysis and actomyosin contractility produce a microscopically porous, flexible basement membrane meshwork for tissue expansion. Cells extend highly active blebs or protrusions towards the surrounding mesenchyme through these perforations. Concurrently, the entire basement membrane undergoes translocation in a direction opposite to bud expansion. Underlying this slowly moving 2D basement membrane translocation are highly dynamic individual cell movements. We conclude this review by describing a variety of exciting research opportunities for discovering novel insights into cell-matrix interactions.
Genetically wired neural mechanisms inhibit mating between species because even naive animals rarely mate with other species. These mechanisms can evolve through changes in expression or function of key genes in sensory pathways or central circuits. Gr32a is a gustatory chemoreceptor that, in D. melanogaster, is essential to inhibit interspecies courtship and sense quinine. Similar to D. melanogaster, we find that D. simulans Gr32a is expressed in foreleg tarsi, sensorimotor appendages that inhibit interspecies courtship, and it is required to sense quinine. Nevertheless, Gr32a is not required to inhibit interspecies mating by D. simulans males. However, and similar to its function in D. melanogaster, Ppk25, a member of the Pickpocket family, promotes conspecific courtship in D. simulans. Together, we have identified distinct evolutionary mechanisms underlying chemosensory control of taste and courtship in closely related Drosophila species.
The rapid advancement of live-cell imaging technologies has enabled biologists to generate high-dimensional data to follow biological movement at the microscopic level. Yet, the "perceived" ease of use of modern microscopes has led to challenges whereby sub-optimal data are commonly generated that cannot support quantitative tracking and analysis as a result of various ill-advised decisions made during image acquisition. Even optimally acquired images often require further optimization through digital processing before they can be analyzed. In writing this article, we presume our target audience to be biologists with a foundational understanding of digital image acquisition and processing, who are seeking to understand the essential steps for particle/object tracking experiments. It is with this targeted readership in mind that we review the basic principles of image-processing techniques as well as analysis strategies commonly used for tracking experiments. We conclude this technical survey with a discussion of how movement behavior can be mathematically modeled and described. © 2019 by John Wiley & Sons, Inc.
We present CLADES (Cell Lineage Access Driven by an Edition Sequence), a technology for cell lineage studies based on CRISPR/Cas9. CLADES relies on a system of genetic switches to activate and inactivate reporter genes in a pre-determined order. Targeting CLADES to progenitor cells allows the progeny to inherit a sequential cascade of reporters, coupling birth order with reporter expression. This gives us temporal resolution of lineage development that can be used to deconstruct an extended cell lineage by tracking the reporters expressed in the progeny. When targeted to the germ line, the same cascade progresses across animal generations, marking each generation with the corresponding combination of reporters. CLADES thus offers an innovative strategy for making programmable cascades of genes that can be used for genetic manipulation or to record serial biological events.
Metabolic coordination between neurons and astrocytes is critical for the health of the brain. However, neuron-astrocyte coupling of lipid metabolism, particularly in response to neural activity, remains largely uncharacterized. Here, we demonstrate that toxic fatty acids (FAs) produced in hyperactive neurons are transferred to astrocytic lipid droplets by ApoE-positive lipid particles. Astrocytes consume the FAs stored in lipid droplets via mitochondrial β-oxidation in response to neuronal activity and turn on a detoxification gene expression program. Our findings reveal that FA metabolism is coupled in neurons and astrocytes to protect neurons from FA toxicity during periods of enhanced activity. This coordinated mechanism for metabolizing FAs could underlie both homeostasis and a variety of disease states of the brain.
There is increased appreciation that dopamine neurons in the midbrain respond not only to reward1 and reward-predicting cues1,2, but also to other variables such as the distance to reward3, movements4,5,6,7,8,9 and behavioural choices10,11. An important question is how the responses to these diverse variables are organized across the population of dopamine neurons. Whether individual dopamine neurons multiplex several variables, or whether there are subsets of neurons that are specialized in encoding specific behavioural variables remains unclear. This fundamental question has been difficult to resolve because recordings from large populations of individual dopamine neurons have not been performed in a behavioural task with sufficient complexity to examine these diverse variables simultaneously. Here, to address this gap, we used two-photon calcium imaging through an implanted lens to record the activity of more than 300 dopamine neurons from the ventral tegmental area of the mouse midbrain during a complex decision-making task. As mice navigated in a virtual-reality environment, dopamine neurons encoded an array of sensory, motor and cognitive variables. These responses were functionally clustered, such that subpopulations of neurons transmitted information about a subset of behavioural variables, in addition to encoding reward. These functional clusters were spatially organized, with neighbouring neurons more likely to be part of the same cluster. Together with the topography between dopamine neurons and their projections, this specialization and anatomical organization may aid downstream circuits in correctly interpreting the wide range of signals transmitted by dopamine neurons.