A5028427533- Wnt/β-catenin signaling in development and cancer
- Axon Guidance and Neuronal Signaling
- Neuroscience and Neuropharmacology Research
- RNA Research and Splicing
- Sphingolipid Metabolism and Signaling
- Neurogenesis and neuroplasticity mechanisms
- Lipid Membrane Structure and Behavior
- Developmental Biology and Gene Regulation
- Neuroendocrine regulation and behavior
- Cancer-related gene regulation
- Receptor Mechanisms and Signaling
- Cellular transport and secretion
- Hippo pathway signaling and YAP/TAZ
- MicroRNA in disease regulation
- Nerve injury and regeneration
- Sleep and Wakefulness Research
- Neuroinflammation and Neurodegeneration Mechanisms
- CRISPR and Genetic Engineering
- Autism Spectrum Disorder Research
- Ion channel regulation and function
- Genetics and Neurodevelopmental Disorders
- Cellular Mechanics and Interactions
- Circadian rhythm and melatonin
- Pluripotent Stem Cells Research
- Retinal Development and Disorders
University of Iowa
2016-2025
University of California, Los Angeles
2024
Columbia University
2024
Iowa City Public Library
2021
Tokushima University
2019
Delta Air Lines (United States)
2015
Max Delbrück Center
2011
University of British Columbia
2011
Albert Einstein College of Medicine
2011
Yeshiva University
2011
Neocortical neuroblast cell lines were used to clone G-protein-coupled receptor (GPCR) genes study signaling mechanisms regulating cortical neurogenesis. One putative GPCR gene displayed an in situ expression pattern enriched neurogenic regions and was therefore named ventricular zone gene-1 (vzg-1). The vzg-1 cDNA hybridized a 3.8-kb mRNA transcript encoded protein with predicted molecular mass of 41-42 kD, confirmed by Western blot analysis. To assess its function, overexpressed line from...
Although extracellular application of lysophosphatidic acid (LPA) has been extensively documented to produce a variety cellular responses through family specific G protein-coupled receptors, the in vivo organismal role LPA signaling remains largely unknown. The first identified receptor gene, lp A1 / vzg-1 edg-2 , was previously shown have remarkably enriched embryonic expression cerebral cortex and dorsal olfactory bulb postnatal myelinating glia including Schwann cells. Here, we show that...
Compartmentalization of cAMP-dependent protein kinase is achieved in part by interaction with A-kinase anchoring proteins (AKAPs). All the identified previously target tethering type II regulatory subunit. Here we report cloning and characterization a novel protein, D-AKAP1, that interacts N terminus both I subunits. A cDNA encoding 125-amino acid fragment D-AKAP1 was isolated from two-hybrid screen shown to interact specifically Although single message 3.8 kilobase pairs detected for all...
Lysophosphatidic acid (LPA) is a bioactive phospholipid with properties of an extracellular growth factor for many cell lines, including those derived from neuroblastomas. However, the relevance LPA signaling to normal, developing nervous system unknown, in part reflecting previous unavailability cloned receptor genes. Recent studies first such gene, encoding G protein-coupled LP A1 /VZG-1 (lysophospholipid A1/ventricular zone gene-1), revealed major locus expression oligodendrocytes and...
The specificity of interactions between neurons is believed to be mediated by diverse cell adhesion molecules, including members the cadherin superfamily. Whereas mechanisms classical have been studied extensively, much less known about related protocadherins (Pcdhs), which together make up majority Here we use quantitative aggregation assays and biochemical analyses characterize cis trans among 22-member γ-Pcdh family, shown critical for control synaptogenesis neuronal survival. We show...
During central nervous system (CNS) development, programmed cell death (PCD) has been viewed traditionally as a fate reserved for differentiating neurons that are in the process of making synaptic connections. Recent studies embryonic cerebral cortex (Blaschke et al. [1996] Development 122:1165–1174), however, have shown many neuroblasts proliferative ventricular zone undergo PCD well and this likely represents novel form distinct from found regions postmitotic neurons. To determine...
Pbx1 is a homeodomain transcription factor that has the ability to form heterodimers with proteins encoded by homeotic selector (Hox) gene complexes and increase their DNA-binding affinity specificity. A current hypothesis proposes interactions are necessary for Hox regulate downstream target genes in turn control growth, differentiation morphogenesis during development. In pre B cell leukemias containing t(1;19) chromosome translocation, converted into strong transactivator fusion...
Subcellular localization directed by specific A kinase anchoring proteins (AKAPs) is a mechanism for compartmentalization of cAMP-dependent protein (PKA). Using two-hybrid screen, novel AKAP was isolated. Because it interacts with both the type I and II regulatory subunits, defined as dual or D-AKAP1. Here we report cloning characterization another cDNA isolated from that screen. This new member D-AKAP family, D-AKAP2, also binds types subunits. message 5 kb pairs detected D-AKAP2 in all...
Fifty-eight cadherin-related protocadherin (Pcdh) genes are tandemly arrayed in three clusters (alpha, beta, and gamma) on mouse chromosome 18. The large number of clustered Pcdh family members, their presence at synapses, the known binding specificities other cadherin superfamily members all suggest that these Pcdhs play roles specifying synaptic connectivity. Consistent with this idea, mice lacking 22 Pcdh-gamma cluster have decreased numbers spinal cord synapses nearly immobile....
Recent studies indicate that astrocytes, whose processes enwrap synaptic terminals, promote synapse formation both by releasing soluble factors and through contact-dependent mechanisms. Although astrocyte-secreted synaptogenic have been identified, the molecules underlying perisynaptic astroctye–neuron contacts are unknown. Here we show γ-protocadherins (γ-Pcdhs), a family of 22 neuronal adhesion encoded single gene cluster, also expressed astrocytes localize to their processes. Using...
Highlights•Increasing γ-Pcdh homophilic matching promotes dendrite complexity in the cortex•Inducing mismatching reduces cortex•Astrocytes regulate cell non-autonomously via interactions•γ-Pcdhs promote through local interactionsSummaryGrowth of a properly complex arbor is key step neuronal differentiation and prerequisite for neural circuit formation. Diverse surface molecules, such as clustered protocadherins (Pcdhs), have long been proposed to formation specific cell-cell interactions....
Light touch sensation begins with activation of low-threshold mechanoreceptor (LTMR) endings in the skin and propagation their signals to spinal cord brainstem. We found that clustered protocadherin gamma (Pcdhg) gene locus, which encodes 22 cell-surface homophilic binding proteins, is required somatosensory neurons for normal behavioral reactivity a range tactile stimuli. Developmentally, distinct Pcdhg isoforms mediate LTMR synapse formation through neuron-neuron interactions peripheral...
ABSTRACT The γ‐protocadherins (γ‐Pcdhs) comprise 22 homophilic cell adhesion molecule isoforms, expressed from the Pcdhg gene cluster via promoter choice mechanisms that serve many crucial functions during neural development. Emerging evidence supports hypothesis distinct isoforms have unique functions. γC4 isoform, which is Pcdhgc4 and includes its variable exon, sole γ‐Pcdh isoform essential for postnatal survival in mice. Here we describe a new mouse line ( C4‐GFP ) with C‐terminal GFP...
The growth-factor–like phospholipid lysophosphatidic acid (LPA) mediates a wide variety of biological functions. We recently reported the cloning first G-protein–coupled receptor for LPA, called ventricular zone gene-1 (vzg-1/lpA1/edg-2) because its embryonic central nervous system (CNS) expression is restricted to neocortical (Hecht et al. [1996] J. Cell Biol. 135:1071–1083). Vzg-1 neural diminishes at end cortical neurogenetic period, just before birth. Here, we have investigated...
In peripheral nerves, Schwann cells (SCs) form contacts with axons, other SCs, and extracellular matrix components that are critical for their migration, differentiation, response to injury. Here, we report lysophosphatidic acid (LPA), an signaling phospholipid, regulates the morphology adhesion of cultured SCs. Treatment LPA induces f-actin rearrangements resulting in a "wreath"-like structure, actin loops bundled peripherally by short orthogonal filaments. The latter appear anchor SC...
Neurons use kinesin and dynein microtubule-dependent motor proteins to transport essential cellular components along axonal dendritic microtubules. In a search for new kinesin-like proteins, we identified two neuronally enriched mouse kinesins that provide insight into unique intracellular targeting mechanism in neurons. KIF21A KIF21B share colinear amino acid similarity each other, but not any previously outside of the domain. Each protein also contains domain seven WD-40 repeats, which may...