Filter
Associated Lab
- Aguilera Castrejon Lab (1) Apply Aguilera Castrejon Lab filter
- Ahrens Lab (52) Apply Ahrens Lab filter
- Aso Lab (40) Apply Aso Lab filter
- Baker Lab (19) Apply Baker Lab filter
- Betzig Lab (100) Apply Betzig Lab filter
- Beyene Lab (8) Apply Beyene Lab filter
- Bock Lab (14) Apply Bock Lab filter
- Branson Lab (49) Apply Branson Lab filter
- Card Lab (36) Apply Card Lab filter
- Cardona Lab (44) Apply Cardona Lab filter
- Chklovskii Lab (10) Apply Chklovskii Lab filter
- Clapham Lab (13) Apply Clapham Lab filter
- Cui Lab (19) Apply Cui Lab filter
- Darshan Lab (8) Apply Darshan Lab filter
- Dickson Lab (32) Apply Dickson Lab filter
- Druckmann Lab (21) Apply Druckmann Lab filter
- Dudman Lab (38) Apply Dudman Lab filter
- Eddy/Rivas Lab (30) Apply Eddy/Rivas Lab filter
- Egnor Lab (4) Apply Egnor Lab filter
- Espinosa Medina Lab (15) Apply Espinosa Medina Lab filter
- Feliciano Lab (7) Apply Feliciano Lab filter
- Fetter Lab (31) Apply Fetter Lab filter
- Fitzgerald Lab (16) Apply Fitzgerald Lab filter
- Freeman Lab (15) Apply Freeman Lab filter
- Funke Lab (38) Apply Funke Lab filter
- Gonen Lab (59) Apply Gonen Lab filter
- Grigorieff Lab (34) Apply Grigorieff Lab filter
- Harris Lab (50) Apply Harris Lab filter
- Heberlein Lab (13) Apply Heberlein Lab filter
- Hermundstad Lab (22) Apply Hermundstad Lab filter
- Hess Lab (74) Apply Hess Lab filter
- Ilanges Lab (2) Apply Ilanges Lab filter
- Jayaraman Lab (42) Apply Jayaraman Lab filter
- Ji Lab (33) Apply Ji Lab filter
- Johnson Lab (1) Apply Johnson Lab filter
- Karpova Lab (13) Apply Karpova Lab filter
- Keleman Lab (8) Apply Keleman Lab filter
- Keller Lab (61) Apply Keller Lab filter
- Koay Lab (2) Apply Koay Lab filter
- Lavis Lab (136) Apply Lavis Lab filter
- Lee (Albert) Lab (29) Apply Lee (Albert) Lab filter
- Leonardo Lab (19) Apply Leonardo Lab filter
- Li Lab (4) Apply Li Lab filter
- Lippincott-Schwartz Lab (96) Apply Lippincott-Schwartz Lab filter
- Liu (Yin) Lab (1) Apply Liu (Yin) Lab filter
- Liu (Zhe) Lab (57) Apply Liu (Zhe) Lab filter
- Looger Lab (137) Apply Looger Lab filter
- Magee Lab (31) Apply Magee Lab filter
- Menon Lab (12) Apply Menon Lab filter
- Murphy Lab (6) Apply Murphy Lab filter
- O'Shea Lab (5) Apply O'Shea Lab filter
- Otopalik Lab (1) Apply Otopalik Lab filter
- Pachitariu Lab (35) Apply Pachitariu Lab filter
- Pastalkova Lab (5) Apply Pastalkova Lab filter
- Pavlopoulos Lab (7) Apply Pavlopoulos Lab filter
- Pedram Lab (4) Apply Pedram Lab filter
- Podgorski Lab (16) Apply Podgorski Lab filter
- Reiser Lab (45) Apply Reiser Lab filter
- Riddiford Lab (20) Apply Riddiford Lab filter
- Romani Lab (31) Apply Romani Lab filter
- Rubin Lab (105) Apply Rubin Lab filter
- Saalfeld Lab (46) Apply Saalfeld Lab filter
- Satou Lab (1) Apply Satou Lab filter
- Scheffer Lab (36) Apply Scheffer Lab filter
- Schreiter Lab (50) Apply Schreiter Lab filter
- Sgro Lab (1) Apply Sgro Lab filter
- Shroff Lab (31) Apply Shroff Lab filter
- Simpson Lab (18) Apply Simpson Lab filter
- Singer Lab (37) Apply Singer Lab filter
- Spruston Lab (57) Apply Spruston Lab filter
- Stern Lab (73) Apply Stern Lab filter
- Sternson Lab (47) Apply Sternson Lab filter
- Stringer Lab (32) Apply Stringer Lab filter
- Svoboda Lab (131) Apply Svoboda Lab filter
- Tebo Lab (9) Apply Tebo Lab filter
- Tervo Lab (9) Apply Tervo Lab filter
- Tillberg Lab (18) Apply Tillberg Lab filter
- Tjian Lab (17) Apply Tjian Lab filter
- Truman Lab (58) Apply Truman Lab filter
- Turaga Lab (39) Apply Turaga Lab filter
- Turner Lab (26) Apply Turner Lab filter
- Vale Lab (7) Apply Vale Lab filter
- Voigts Lab (3) Apply Voigts Lab filter
- Wang (Meng) Lab (20) Apply Wang (Meng) Lab filter
- Wang (Shaohe) Lab (6) Apply Wang (Shaohe) Lab filter
- Wu Lab (8) Apply Wu Lab filter
- Zlatic Lab (26) Apply Zlatic Lab filter
- Zuker Lab (5) Apply Zuker Lab filter
Associated Project Team
- CellMap (12) Apply CellMap filter
- COSEM (3) Apply COSEM filter
- FIB-SEM Technology (3) Apply FIB-SEM Technology filter
- Fly Descending Interneuron (11) Apply Fly Descending Interneuron filter
- Fly Functional Connectome (14) Apply Fly Functional Connectome filter
- Fly Olympiad (5) Apply Fly Olympiad filter
- FlyEM (53) Apply FlyEM filter
- FlyLight (49) Apply FlyLight filter
- GENIE (45) Apply GENIE filter
- Integrative Imaging (3) Apply Integrative Imaging filter
- Larval Olympiad (2) Apply Larval Olympiad filter
- MouseLight (18) Apply MouseLight filter
- NeuroSeq (1) Apply NeuroSeq filter
- ThalamoSeq (1) Apply ThalamoSeq filter
- Tool Translation Team (T3) (26) Apply Tool Translation Team (T3) filter
- Transcription Imaging (45) Apply Transcription Imaging filter
Associated Support Team
- Project Pipeline Support (4) Apply Project Pipeline Support filter
- Anatomy and Histology (18) Apply Anatomy and Histology filter
- Cryo-Electron Microscopy (34) Apply Cryo-Electron Microscopy filter
- Electron Microscopy (15) Apply Electron Microscopy filter
- Gene Targeting and Transgenics (11) Apply Gene Targeting and Transgenics filter
- Integrative Imaging (17) Apply Integrative Imaging filter
- Invertebrate Shared Resource (40) Apply Invertebrate Shared Resource filter
- Janelia Experimental Technology (37) Apply Janelia Experimental Technology filter
- Management Team (1) Apply Management Team filter
- Molecular Genomics (15) Apply Molecular Genomics filter
- Primary & iPS Cell Culture (14) Apply Primary & iPS Cell Culture filter
- Project Technical Resources (49) Apply Project Technical Resources filter
- Quantitative Genomics (19) Apply Quantitative Genomics filter
- Scientific Computing Software (91) Apply Scientific Computing Software filter
- Scientific Computing Systems (7) Apply Scientific Computing Systems filter
- Viral Tools (14) Apply Viral Tools filter
- Vivarium (7) Apply Vivarium filter
Publication Date
- 2025 (106) Apply 2025 filter
- 2024 (217) Apply 2024 filter
- 2023 (159) Apply 2023 filter
- 2022 (167) Apply 2022 filter
- 2021 (175) Apply 2021 filter
- 2020 (177) Apply 2020 filter
- 2019 (177) Apply 2019 filter
- 2018 (206) Apply 2018 filter
- 2017 (186) Apply 2017 filter
- 2016 (191) Apply 2016 filter
- 2015 (195) Apply 2015 filter
- 2014 (190) Apply 2014 filter
- 2013 (136) Apply 2013 filter
- 2012 (112) Apply 2012 filter
- 2011 (98) Apply 2011 filter
- 2010 (61) Apply 2010 filter
- 2009 (56) Apply 2009 filter
- 2008 (40) Apply 2008 filter
- 2007 (21) Apply 2007 filter
- 2006 (3) Apply 2006 filter
2673 Janelia Publications
Showing 231-240 of 2673 resultsThe human cerebral cortex, pivotal for advanced cognitive functions, is composed of six distinct layers and dozens of functionally specialized areas. The layers and areas are distinguished both molecularly, by diverse neuronal and glial cell subtypes, and structurally, through intricate spatial organization3,4. While single-cell transcriptomics studies have advanced molecular characterization of human cortical development, a critical gap exists due to the loss of spatial context during cell dissociation. Here, we utilized multiplexed error-robust fluorescence in situ hybridization (MERFISH)9, augmented with deep-learning-based cell segmentation, to examine the molecular, cellular, and cytoarchitectural development of human fetal cortex with spatially resolved single-cell resolution. Our extensive spatial atlas, encompassing 16 million single cells, spans eight cortical areas across four time points in the second and third trimesters. We uncovered an early establishment of the six-layer structure, identifiable in the laminar distribution of excitatory neuronal subtypes by mid-gestation, long before the emergence of cytoarchitectural layers. Notably, while anterior-posterior gradients of neuronal subtypes were generally observed in most cortical areas, a striking exception was the sharp molecular border between primary (V1) and secondary visual cortices (V2) at gestational week 20. Here we discovered an abrupt binary shift in neuronal subtype specification at the earliest stages, challenging the notion that continuous morphogen gradients dictate mid-gestation cortical arealization. Moreover, integrating single-nuclei RNA-sequencing and in situ whole transcriptomics revealed an early upregulation of synaptogenesis in V1-specific Layer 4 neurons, suggesting a role of synaptogenesis in this discrete border formation. Collectively, our findings underscore the crucial role of spatial relationships in determining the molecular specification of cortical layers and areas. This work not only provides a valuable resource for the field, but also establishes a spatially resolved single-cell analysis paradigm that paves the way for a comprehensive developmental atlas of the human brain. Preprint: https://www.biorxiv.org/content/early/2024/06/10/2024.06.05.597673
Centrioles organize centrosomes, the cell's primary microtubule-organizing centers (MTOCs). Centrioles double in number each cell cycle, and mis-regulation of this process is linked to diseases such as cancer and microcephaly. In C. elegans, centriole assembly is controlled by the Plk4 related-kinase ZYG-1, which recruits the SAS-5-SAS-6 complex. While the kinase activity of ZYG-1 is required for centriole assembly, how it functions has not been established. Here we report that ZYG-1 physically interacts with and phosphorylates SAS-5 on 17 conserved serine and threonine residues in vitro. Mutational scanning reveals that serine 10 and serines 331/338/340 are indispensable for proper centriole assembly. Embryos expressing SAS-5 exhibit centriole assembly failure, while those expressing SAS-5 possess extra centrioles. We show that in the absence of serine 10 phosphorylation, the SAS-5-SAS-6 complex is recruited to centrioles, but is not stably incorporated, possibly due to a failure to coordinately recruit the microtubule-binding protein SAS-4. Our work defines the critical role of phosphorylation during centriole assembly and reveals that ZYG-1 might play a role in preventing the formation of excess centrioles.
Single-molecule localization microscopy (SMLM) uses activatable or switchable fluorophores to create non-diffraction limited maps of molecular location in biological samples. Despite the utility of this imaging technique, the portfolio of appropriate labels for SMLM remains limited. Here, we describe a general strategy for the construction of “glitter bomb” labels by simply combining rhodamine and coumarin dyes though an amide bond. Condensation of the ortho-carboxyl group on the pendant phenyl ring of rhodamine dyes with a 7-aminocoumarin yields photochromic or spontaneously blinking fluorophores depending on the parent rhodamine structure. We apply this strategy to prepare labels useful super-resolution experiments in fixed cells using different attachment techniques. This general glitter bomb strategy should lead to improved labels for SMLM, ultimately enabling the creation of detailed molecular maps in biological samples.
All multicellular systems produce and dynamically regulate extracellular matrices (ECM) that play important roles in both biochemical and mechanical signaling. Though the spatial arrangement of these extracellular assemblies is critical to their biological functions, visualization of ECM structure is challenging, in part because the biomolecules that compose the ECM are difficult to fluorescently label individually and collectively. Here, we present a cell-impermeable small molecule fluorophore, termed Rhobo6, that turns on and red shifts upon reversible binding to glycans. Given that most ECM components are densely glycosylated, the dye enables wash-free visualization of ECM, in systems ranging from in vitro substrates to in vivo mouse mammary tumors. Relative to existing techniques, Rhobo6 provides a broad substrate profile, superior tissue penetration, nonperturbative labeling, and negligible photobleaching. This work establishes a straightforward method for imaging the distribution of ECM in live tissues and organisms, lowering barriers for investigation of extracellular biology.
The hepatocytes within the liver present an immense capacity to adapt to changes in nutrient availability. Here, by using high resolution volume electron microscopy, we map how hepatic subcellular spatial organization is regulated during nutritional fluctuations and as a function of liver zonation. We identify that fasting leads to remodeling of endoplasmic reticulum (ER) architecture in hepatocytes, characterized by the induction of single rough ER sheet around the mitochondria, which becomes larger and flatter. These alterations are enriched in periportal and mid-lobular hepatocytes but not in pericentral hepatocytes. Gain- and loss-of-function in vivo models demonstrate that the Ribosome receptor binding protein1 (RRBP1) is required to enable fasting-induced ER sheet-mitochondria interactions and to regulate hepatic fatty acid oxidation. Endogenous RRBP1 is enriched around periportal and mid-lobular regions of the liver. In obesity, ER-mitochondria interactions are distinct and fasting fails to induce rough ER sheet-mitochondrion interactions. These findings illustrate the importance of a regulated molecular architecture for hepatocyte metabolic flexibility.
Third-harmonic generation microscopy is a powerful label-free nonlinear imaging technique, providing essential information about structural characteristics of cells and tissues without requiring external labelling agents. In this work, we integrated a recently developed compact adaptive optics module into a third-harmonic generation microscope, to measure and correct for optical aberrations in complex tissues. Taking advantage of the high sensitivity of the third-harmonic generation process to material interfaces and thin membranes, along with the 1,300-nm excitation wavelength used here, our adaptive optical third-harmonic generation microscope enabled high-resolution in vivo imaging within highly scattering biological model systems. Examples include imaging of myelinated axons and vascular structures within the mouse spinal cord and deep cortical layers of the mouse brain, along with imaging of key anatomical features in the roots of the model plant Brachypodium distachyon. In all instances, aberration correction led to significant enhancements in image quality.
Across the cell cycle, mitochondrial dynamics are regulated by a cycling wave of actin polymerization/depolymerization. In metaphase, this wave induces actin comet tails on mitochondria that propel these organelles to drive spatial mixing, resulting in their equitable inheritance by daughter cells. In contrast, during interphase the cycling actin wave promotes localized mitochondrial fission. Here, we identify the F-actin nucleator/elongator FMNL1 as a positive regulator of the wave. FMNL1-depleted cells exhibit decreased mitochondrial polarization, decreased mitochondrial oxygen consumption, and increased production of reactive oxygen species. Accompanying these changes is a loss of hetero-fusion of wave-fragmented mitochondria. Thus, we propose that the interphase actin wave maintains mitochondrial homeostasis by promoting mitochondrial content mixing. Finally, we investigate the mechanistic basis for the observation that the wave drives mitochondrial motility in metaphase but mitochondrial fission in interphase. Our data indicate that when the force of actin polymerization is resisted by mitochondrial tethering to microtubules, as in interphase, fission results.
Stereocilia are unidirectional F-actin-based cylindrical protrusions on the apical surface of inner ear hair cells and function as biological mechanosensors of sound and acceleration. Development of functional stereocilia requires motor activities of unconventional myosins to transport proteins necessary for elongating the F-actin cores and to assemble the mechanoelectrical transduction (MET) channel complex. However, how each myosin localizes in stereocilia using the energy from ATP hydrolysis is only partially understood. In this study, we develop a methodology for live-cell single-molecule fluorescence microscopy of organelles protruding from the apical surface using a dual-view light-sheet microscope, diSPIM. We demonstrate that MYO7A, a component of the MET machinery, traffics as a dimer in stereocilia. Movements of MYO7A are restricted when scaffolded by the plasma membrane and F-actin as mediated by MYO7A’s interacting partners. Here, we discuss the technical details of our methodology and its future applications including analyses of cargo transportation in various organelles.
High-resolution electron microscopy of nervous systems has enabled the reconstruction of synaptic connectomes. However, we do not know the synaptic sign for each connection (i.e., whether a connection is excitatory or inhibitory), which is implied by the released transmitter. We demonstrate that artificial neural networks can predict transmitter types for presynapses from electron micrographs: a network trained to predict six transmitters (acetylcholine, glutamate, GABA, serotonin, dopamine, octopamine) achieves an accuracy of 87% for individual synapses, 94% for neurons, and 91% for known cell types across a D. melanogaster whole brain. We visualize the ultrastructural features used for prediction, discovering subtle but significant differences between transmitter phenotypes. We also analyze transmitter distributions across the brain and find that neurons that develop together largely express only one fast-acting transmitter (acetylcholine, glutamate, or GABA). We hope that our publicly available predictions act as an accelerant for neuroscientific hypothesis generation for the fly.
Although mesenchyme is essential for inducing the epithelium of ectodermal organs, its precise role in organ-specific epithelial fate determination remains poorly understood. To elucidate the roles of tissue interactions in cellular differentiation, we performed single-cell RNA sequencing and imaging analyses on recombined tissues, where mesenchyme and epithelium were switched ex vivo between two types of embryonic mouse salivary glands: the parotid gland (a serous gland) and the submandibular gland (a predominantly mucous gland). We found partial induction of molecules that define gland-specific acinar and myoepithelial cells in recombined salivary epithelium. The parotid epithelium recombined with submandibular mesenchyme began to express mucous acinar genes not intrinsic to the parotid gland. While myoepithelial cells do not normally line parotid acini, newly induced myoepithelial cells densely populated recombined parotid acini. However, mucous acinar and myoepithelial markers continued to be expressed in submandibular epithelial cells recombined with parotid mesenchyme. Consequently, some epithelial cells appeared to be plastic, such that their fate could still be modified in response to mesenchymal signaling, whereas other epithelial cells appeared to be already committed to a specific fate. We also discovered evidence for bidirectional induction: transcriptional changes were observed not only in the epithelium but also in the mesenchyme after heterotypic tissue recombination. For example, parotid epithelium induced the expression of muscle-related genes in submandibular fibroblasts that began to mimic parotid fibroblast gene expression. These studies provide the first comprehensive unbiased molecular characterization of tissue recombination approaches exploring the regulation of cell fate.