A5072249960- Developmental Biology and Gene Regulation
- Neurogenesis and neuroplasticity mechanisms
- Hedgehog Signaling Pathway Studies
- Zebrafish Biomedical Research Applications
- Epigenetics and DNA Methylation
- Axon Guidance and Neuronal Signaling
- Wnt/β-catenin signaling in development and cancer
- Nerve injury and regeneration
- Pluripotent Stem Cells Research
- Congenital heart defects research
- Craniofacial Disorders and Treatments
- Nasal Surgery and Airway Studies
- Histone Deacetylase Inhibitors Research
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Cancer-related gene regulation
- Spinal Cord Injury Research
- Toxin Mechanisms and Immunotoxins
- Cancer-related Molecular Pathways
- Ion channel regulation and function
- Barrier Structure and Function Studies
- Monoclonal and Polyclonal Antibodies Research
- Anatomy and Medical Technology
- Congenital Ear and Nasal Anomalies
- bioluminescence and chemiluminescence research
Rutgers, The State University of New Jersey
2008-2022
Rutgers Health
2021
Johnson University
2006-2020
Rutgers Sexual and Reproductive Health and Rights
2018-2019
Howard Hughes Medical Institute
1998-2000
New York University
1997-2000
NYU Langone Health
1998
National Institutes of Health
1998
National Institute of Neurological Disorders and Stroke
1998
University of Pittsburgh
1996
ABSTRACT The secreted factor Sonic hedgehog (SHH) is both required for and sufficient to induce multiple developmental processes, including ventralization of the CNS, branching morphogenesis lungs anteroposterior patterning limbs. Based on analogy Drosophila Hh pathway, GLI transcription factors in vertebrates are likely transduce SHH signaling repress Shh transcription. In order discriminate between overlapping versus unique requirements three Gli genes mice, we have produced a Gli1 mutant...
ABSTRACT Induction of the floor plate at ventral midline neural tube is one earliest events in establishment dorsoventral (d/v) polarity vertebrate central nervous system (CNS). The secreted molecule, Sonic hedgehog, has been shown to be both necessary and sufficient for this induction. In vertebrates, several downstream components signalling pathway have identified, including members Gli transcription factor family. study, we examined d/v patterning CNS Gli2 mouse mutants. We found that...
The three vertebrate Gli proteins play a central role in mediating Hedgehog(Hh)-dependent cell fate specification the developing spinal cord; however,their individual contributions to this process have not been fully characterized. In paper, we addressed issue by examining patterning cord of Gli2;Gli3 double mutant embryos, and chick embryos transfected with dominant activator forms Gli2 Gli3. homozygotes, Gli1 is also expressed; thus, all protein activities are absent these mice. We show...
Cell fate specification in the CNS is controlled by secreted morphogen sonic hedgehog (Shh). At spinal cord levels, Shh produced both notochord and floor plate (FP) diffuses dorsally to organize patterned gene expression dividing neural glial progenitors. Despite fact that two discrete sources of are involved this process, individual contribution FP, only intrinsic source throughout neurogenesis gliogenesis, has not been clearly defined. Here, we have used conditional mutagenesis approaches...
The vertebrate spinal cord has long served as a useful system for studying the pattern of cell differentiation along dorsoventral (d/v) axis. In this paper, we have defined expression several classes genes expressed in restricted d/v domains intermediate region (IR) mouse cord, which most interneurons are generated. From analysis, found that and their precursors express unique combinations transcription factors Notch ligands at onset differentiation. number different share similar...
The deployment of morphogen gradients is a core strategy to establish cell diversity in developing tissues, but little known about how small differences the concentration extracellular signals are translated into robust patterning output responding cells. We have examined activity homeodomain proteins, which presumed operate downstream graded Shh signaling neural patterning, and describe feedback circuit between pathway transcription factors that establishes non-graded regulation activity....
In caudal regions of the diencephalon, sonic hedgehog (Shh) is expressed in ventral midline prosomeres 1-3 (p1-p3), which underlie pretectum, thalamus and prethalamus, respectively. Shh also zona limitans intrathalamica (zli), a dorsally projecting spike that forms at p2-p3 boundary. The presence two signaling centers has made it difficult to determine specific roles either one regional patterning neuronal fate specification. To investigate requirement from focal source expression we used...
Neuronal subtype diversification is essential for the establishment of functional neural circuits, and yet molecular events underlying neuronal diversity remain largely to be defined. During spinal neurogenesis, p2 progenitor domain, unlike others in ventral cord, gives rise two intermingled but molecularly distinct subtypes interneurons, termed V2a V2b. We show here that Foxn4 winged helix/forkhead transcription factor coexpressed with bHLH Mash1 a subset progenitors. Loss function...
Facial shape is the basis for facial recognition and categorization. features reflect underlying geometry of skeletal structures. Here, we reveal that cartilaginous nasal capsule (corresponding to upper jaw face) shaped by signals generated neural structures: brain olfactory epithelium. Brain-derived Sonic Hedgehog (SHH) enables induction septum posterior capsule, whereas formation a roof controlled from Unexpectedly, cartilage turned out be important shaping membranous bones during...
ABSTRACT When 3-4 segments of the chick lumbosacral neural tube are reversed in anterior-posterior axis at stage 15 (embryonic day 2.5), spinal cord develops with a organization motoneurons projecting to individual muscles limb (C. Lance-Jones and L. Landmesser (1980) J. Physiol. 302, 581-602). This finding indicated that motoneuron precursors or components their local environment were specified respect target by 15. To identify timing this event, we have now assessed projections after...
A number of homeodomain transcription factors have been implicated in controlling the differentiation various types neurons including spinal motoneurons. Some these proteins are also expressed interneurons, but their function is unknown. Progress understanding role interneuronal development has slow because synaptic connections which part define identity, difficult to establish. Using whole cell recording isolated cord chick embryos, we assessed lumbosacral interneurons expressing...
Within the developing vertebrate spinal cord, motor neuron subtypes are distinguished by settling positions of their cell bodies, patterns gene expression, and paths axons follow to exit CNS. The inclusive set cues required guide a given axon subtype from body target has yet be identified, in any species. This is attributable, part, unavailability markers that demarcate complete trajectory followed specific class axons. Most neurons extend out CNS through ventral points. In contrast,...
Abstract Proper central nervous system (CNS) function depends critically on the generation of functionally distinct neuronal types in specific and reproducible positions. The diversity during CNS development involves a fine balance between dividing neural progenitors differentiated progeny that they produce. However, molecular mechanisms regulate these processes are still poorly understood. Here, we show Prox1 transcription factor, which is expressed transiently specifically spinal...
During neural tube development, Shh signaling through Gli transcription factors is necessary to establish five distinct ventral progenitor domains that give rise unique classes of neurons and glia arise in specific positions along the dorsoventral axis. These cells are generated from progenitors display factor gene expression profiles ventricular zone. However, molecular genetic mechanisms control differential spatiotemporal transcriptional responses target genes graded Shh-Gli remain...
During development of the ventral spinal cord, V2 interneurons emerge from p2 progenitors and diversify into two major subtypes, V2a V2b, that play key roles in locomotor coordination. Dll4-mediated Notch activation a subset precursors constitutes crucial first step towards generating neuronal diversity this domain. The mechanism behind asymmetric downstream signaling events are, however, unknown at present. We show here Ascl1 Neurog basic helix-loop-helix (bHLH) proneural factors are...
ABSTRACT Background: All vertebrate peripheral nerves connect the central nervous system (CNS) with targets in periphery and are composed of axons, layers ensheathing glia connective tissue. Although structure these conduits is well established, very little known about origin developmental roles some their elements. One understudied component, perineurium, ensheaths nerve fascicles a component blood‐nerve‐barrier. In zebrafish, motor perineurium CNS‐derived nkx2.2a + perineurial glia, which...
Abstract Specialized cells at the midline of central nervous system have been implicated in controlling axon projections both invertebrates and vertebrates. To address requirement for ventral providing cues to commissural axons mice, we analyzed Gli2 mouse mutants, which lack specifically floor plate immediately adjacent interneurons. We show that a Dbx1 enhancer drives tau-lacZ expression subpopulation and, using reporter line generated from this construct, as well DiI tracing, find...