A5000064890- Neuroscience of respiration and sleep
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Developmental Biology and Gene Regulation
- Pluripotent Stem Cells Research
- Neuroendocrine regulation and behavior
- Congenital heart defects research
- CRISPR and Genetic Engineering
- Animal Genetics and Reproduction
- Neuroscience and Neuropharmacology Research
- Heart Rate Variability and Autonomic Control
- Neural dynamics and brain function
- Sleep and Wakefulness Research
- Zebrafish Biomedical Research Applications
- Cellular transport and secretion
- Axon Guidance and Neuronal Signaling
- Neonatal Respiratory Health Research
- Neurogenesis and neuroplasticity mechanisms
- Circadian rhythm and melatonin
- Neuroinflammation and Neurodegeneration Mechanisms
- Nicotinic Acetylcholine Receptors Study
- Immune Cell Function and Interaction
- Ubiquitin and proteasome pathways
- Traumatic Brain Injury and Neurovascular Disturbances
- T-cell and B-cell Immunology
Harvard University
2015-2024
Boston VA Research Institute
2021-2024
Howard Hughes Medical Institute
1991-2016
Brigham and Women's Hospital
2016
University of Pennsylvania
1985-2012
California Institute for Regenerative Medicine
2012
Harvard University Press
2008
Carnegie Institution for Science
1996
Carnegie Observatories
1996
Department of Embryology
1996
Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and publicly available genome-wide collection mouse knockouts would be significantly enabling for biomedical discovery. To date, published exist only about 10% genes. Furthermore, many these are limited utility because they have not been made or phenotyped standardized ways, freely to researchers. It is time harness new technologies efficiencies production mount high-throughput international effort...
As conditional genetic strategies advance, the need for multiple site-specific recombinase systems has emerged. To meet this in part, we have targeted constitutive ROSA26 locus to create a mouse strain with generalized expression of enhanced version FLP (FLPe). This is designated FLPeR ("flipper"). Using strain, extensive target gene recombination can be achieved most tissue types, including cells developing germ line. mice therefore serve two important functions: as source many different...
Physiological homeostasis is essential for organism survival. Highly responsive neuronal networks are involved, but their constituent neurons just beginning to be resolved. To query brain serotonergic in homeostasis, we used a silencing tool, mouse RC::FPDi (based on the synthetic G protein-coupled receptor Di), designed cell type-specific, ligand-inducible, and reversible suppression of action potential firing. In mice harboring Di-expressing neurons, administration ligand clozapine-N-oxide...
Exploiting nervous paths already traveled The parasympathetic system helps regulate the functions of many tissues and organs, including salivary glands esophagus. To do so, it needs to reach throughout body, connecting central systems peripheral ones. Dyachuk et al. Espinosa-Medina explored how these connections are established in mice (see Perspective by Kalcheim Rohrer). Progenitor cells that travel along with developing nerves can give rise both myelinforming Schwann neurons. That means...
Site-specific recombinases are being developed as tools for "in vivo" genetic engineering because they can catalyze precise excisions, integrations, inversions, or translocations of DNA between their distinct recognition target sites. Here it is demonstrated that Flp recombinase effectively mediate site-specific excisional recombination in mouse embryonic stem cells, differentiating embryonal carcinoma and transgenic mice. Broad expression compatible with normal development, suggesting be...
Several pathways of transmembrane signaling in lymphocytes involve protein-tyrosine phosphorylation. With the exception p56 lck , a tyrosine kinase specific to T lymphoid cells that associates with cell proteins CD4 and CD8, kinases function these are unknown. A murine lymphocyte complementary DNA represents new member src family has now been isolated characterized. This DNA, termed blk (for B kinase), specifies polypeptide 55 kilodaltons is related to, but distinct from, previously...
ABSTRACT In this study, we use a mouse insertional mutant to delineate gene activities that shape the distal limb skeleton. A recessive mutation results in brachydactyly was found lineage of transgenic mice. Sequences flanking transgene insertion site were cloned, mapped chromosome 3, and used identify as type IB bone morphogenetic protein receptor, BmprIB (ALK6). Expression analyses wild-type mice revealed two major classes transcripts. Rather than representing unique coding RNAs generated...
Heterotopic ossification (HO), the abnormal formation of true marrow-containing bone within extraskeletal soft tissues, is a serious bony disorder that may be either acquired or hereditary. We utilized an animal model genetic fibrodysplasia ossificans progressiva to examine cellular mechanisms underlying HO. found HO in these animals was triggered by tissue injuries and effects were mediated macrophages. Spreading beyond initial injury site adaptive immune system. These observations suggest...
Abstract Brain serotonin neurons are heterogeneous and can be distinguished by several anatomical physiological characteristics. Toward resolving this heterogeneity into classes of functional relevance, subtypes mature were previously identified based on gene expression differences initiated during development in different rhombomeric (r) segments the hindbrain. This redefinition neuron criteria genetic lineage, along with enabling fate mapping tools, now allows various properties, such as...
V1 and V2b interneurons (INs) are essential for the production of an alternating flexor-extensor motor output. Using a tripartite genetic system to selectively ablate either or INs in caudal spinal cord assess their specific functions awake behaving animals, we find that function opposing manner control flexor-extensor-driven movements. Ablation results limb hyperflexion, suggesting IN-derived inhibition is needed proper extension movements limb. The loss hindlimb hyperextension delay...
Islet1 (Isl1) has been proposed as a marker of cardiac progenitor cells derived from the second heart field and is utilized to identify purify progenitors murine human specimens for ex vivo expansion. The use Isl1 specific dependent on its exclusion other lineages such neural crest.Determine whether expressed by crest.We used an intersectional fate-mapping system using RC::FrePe allele, which reports dual Flpe Cre recombination. Combining Isl1(Cre/+), SHF driver, Wnt1::Flpe, crest with...
Serotonergic neurons modulate behavioral and physiological responses from aggression anxiety to breathing thermoregulation. Disorders involving serotonin (5HT) dysregulation are commensurately heterogeneous numerous. We hypothesized that this breadth in functionality derives part a developmentally determined substructure of distinct subtypes 5HT each specialized specific behaviors. By manipulating defined subgroups one by chemogenetically, we find the Egr2-Pet1 subgroup is drive increased...
Escalated aggression can have devastating societal consequences, yet underlying neurobiological mechanisms are poorly understood. Here, we show significantly increased inter-male mouse when neurotransmission is constitutively blocked from either of two subsets serotonergic, Pet1+ neurons: one identified by dopamine receptor D1(Drd1a)::cre-driven activity perinatally, and the other Drd2::cre pre-adolescence onward. Blocking neuron similar size and/or overlapping anatomical domains had no...
Among the brainstem raphe nuclei, dorsal nucleus (DR) contains greatest number of Pet1-lineage neurons, a predominantly serotonergic group distributed throughout DR subdomains. These neurons collectively regulate diverse physiology and behavior are often therapeutically targeted to treat affective disorders. Characterizing Pet1 neuron molecular heterogeneity relating it anatomy is vital for understanding functional organization, with potential inform therapeutic separability. Here we use...