34 Works

Data from: High-throughput synapse-resolving two-photon fluorescence microendoscopy for deep-brain volumetric imaging in vivo

Guanghan Meng, Yajie Liang, Sarah Sarsfield, Wan-Chen Jiang, Rongwen Lu, Joshua Tate Dudman, Yeka Aponte & Na Ji
Optical imaging has become a powerful tool for studying brains in vivo. The opacity of adult brains makes microendoscopy, with an optical probe such as a gradient index (GRIN) lens embedded into brain tissue to provide optical relay, the method of choice for imaging neurons and neural activity in deeply buried brain structures. Incorporating a Bessel focus scanning module into two-photon fluorescence microendoscopy, we extended the excitation focus axially and improved its lateral resolution. Scanning...

A phase-separated nuclear GBPL circuit controls immunity in plants

Shuai Huang, Shiwei Zhu, Pradeep Kumar & John MacMicking
Liquid-liquid phase separation (LLPS) has emerged as a central paradigm for understanding how membrane-less organelles compartmentalize diverse cellular activities in eukaryotes. Here, we identified a new superfamily of plant Guanylate-Binding Protein-Like GTPases (GBPLs) that assemble LLPS-driven condensates within the nucleus to protect against infection and autoimmunity. In Arabidopsis thaliana, two family members - GBPL1 and GBPL3 - undergo phase transition behavior to control transcriptional responses as part of an allosteric switch triggered by exposure to...

Data from: A genetic signature of the evolution of loss of flight in the Galapagos cormorant

Alejandro Burga, Wang Weiguang, Eyal Ben-David, Paul C. Wolf, Andrew M. Ramey, Claudio Verdugo, Karen Lyons, Patricia G. Parker & Leonid Kruglyak
We have a limited understanding of the genetic and molecular basis of evolutionary changes in the size and proportion of limbs. We studied wing and pectoral skeleton reduction leading to flightlessness in the Galapagos cormorant (Phalacrocorax harrisi). We sequenced and de novo assembled the genomes of four cormorant species and applied a predictive and comparative genomics approach to find candidate variants that may have contributed to the evolution of flightlessness. These analyses and cross-species experiments...

Data from: Identification of a transporter complex responsible for the cytosolic entry of nitrogen-containing-bisphosphonates

Zhou Yu, Lauren E. Surface, Chong Yon Park, Max A Horlbeck, Gregory A Wyant, Monther Abu-Remaileh, Timothy R. Peterson, David M. Sabatini, Jonathan S. Weissman & Erin K. O'Shea
Nitrogen-containing-bisphosphonates (N-BPs) are widely prescribed to treat osteoporosis and other bone-related diseases. Although previous studies established that N-BPs function by inhibiting the mevalonate pathway in osteoclasts, the mechanism by which N-BPs enter the cytosol from the extracellular space to reach their molecular target is not understood. Here we implemented a CRISPRi-mediated genome-wide screen and identified SLC37A3 (solute carrier family 37 member A3) as a gene required for the action of N-BPs in mammalian cells. We...

Data from: Developmental mechanisms of stripe patterns in rodents

Ricardo Mallarino, Corneliu Henegar, Mercedes Mirasierra, Marie Manceau, Carsten Schradin, Mario Vallejo, Slobodan Beronja, Gregory S. Barsh & Hopi E. Hoekstra
Mammalian colour patterns are among the most recognizable characteristics found in nature and can have a profound impact on fitness. However, little is known about the mechanisms underlying the formation and subsequent evolution of these patterns. Here we show that, in the African striped mouse (Rhabdomys pumilio), periodic dorsal stripes result from underlying differences in melanocyte maturation, which give rise to spatial variation in hair colour. We identify the transcription factor ALX3 as a regulator...

Data from: The kinetochore prevents centromere-proximal crossover recombination during meiosis

Nadine Vincenten, Lisa-Marie Kuhl, Isabel Lam, Ashwini Oke, Alastair R. W. Kerr, Andreas Hochwagen, Jennifer C. Fung, Scott Keeney, Gerben Vader & Adèle L. Marston
During meiosis, crossover recombination is essential to link homologous chromosomes and drive 22 faithful chromosome segregation. Crossover recombination is non-random across the genome, 23 and centromere-proximal crossovers are associated with an increased risk of aneuploidy, 24 including Trisomy 21 in humans. Here, we identify the conserved Ctf19/CCAN kinetochore sub- 25 complex as a major factor that minimizes potentially deleterious centromere-proximal crossovers 26 in budding yeast. We uncover multi-layered suppression of pericentromeric recombination by the 27...

Data from: Molecular, spatial and functional single-cell profiling of the hypothalamic preoptic region

Jeffrey R. Moffitt, Dhananjay Bambah-Mukku, Stephen W. Eichhorn, Eric Vaughn, Karthik Shekhar, Julio D. Perez, Nimrod D. Rubinstein, Junjie Hao, Aviv Regev, Catherine Dulac & Xiaowei Zhuang
The hypothalamus controls essential social behaviors and homeostatic functions. However, the cellular architecture of hypothalamic nuclei, including the molecular identity, spatial organization, and function of distinct cell types, is poorly understood. Here, we developed an imaging-based cell type identification and mapping method and combined it with single-cell RNA-sequencing to create a molecularly annotated and spatially resolved cell atlas of the mouse hypothalamic preoptic region. We profiled ~1 million cells, identified ~70 neuronal populations characterized by...

Data from: Engineering ER-stress dependent non-conventional mRNA splicing

Weihan Li, Voytek Okreglak, Jirka Peschek, Philipp Kimmig, Meghan Zubradt, Jonathan S. Weissman & Peter Walter
The endoplasmic reticulum (ER) protein folding capacity is balanced with the protein folding burden to prevent accumulation of un- or misfolded proteins. The ER membrane-resident kinase/RNase Ire1 maintains ER protein homeostasis through two fundamentally distinct processes. First, Ire1 can initiate a transcriptional response through a non-conventional mRNA splicing reaction to increase the ER folding capacity. Second, Ire1 can decrease the ER folding burden through selective mRNA decay. In Saccharomyces cerevisiae and Schizosaccharomyces pombe, the two...

Data from: Nuclear microenvironments modulate transcription from low-affinity enhancers

Albert Tsai, Anand K. Muthusamy, Mariana R. P. Alves, Luke D. Lavis, Robert H. Singer, David L. Stern, Justin Crocker & Mariana RP Alves
Transcription factors bind low-affinity DNA sequences for only short durations. It is not clear how brief, low-affinity interactions can drive efficient transcription. Here we report that the transcription factor Ultrabithorax (Ubx) utilizes low-affinity binding sites in the Drosophila melanogaster shavenbaby (svb) locus and related enhancers in nuclear microenvironments of high Ubx concentrations. Related enhancers colocalize to the same microenvironments independently of their chromosomal location, suggesting that microenvironments are highly differentiated transcription domains. Manipulating the affinity...

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Affiliations

  • Howard Hughes Medical Institute
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