Benjamin W Lindsey

University of Toronto, Toronto, Ontario, Canada

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Publications (7)26.49 Total impact

  • Benjamin W Lindsey, Audrey Darabie, Vincent Tropepe
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    ABSTRACT: A central goal of adult neurogenesis research is to characterize the cellular constituents of a neurogenic niche and to understand how these cells regulate the production of new neurons. Because the generation of adult-born neurons may be tightly coupled to their functional requirement, the organization and output of neurogenic niches may vary across different regions of the brain or between species. We have undertaken a comparative study of six (D, Vd, Vv, Dm, Dl, Ppa) periventricular zones (PVZs) harboring proliferative cells present in the adult forebrain of the zebrafish (Danio rerio), a species known to possess widespread neurogenesis throughout life. Using electron microscopy, we have documented for the first time the detailed cytoarchitecture of these zones, and propose a model of the cellular composition of pallial and subpallial PVZs, as well as a classification scheme for identifying morphologically distinct cell types. Immunolabeling of resin-embedded tissue confirmed the phenotype of three constitutively proliferating (bromodeoxyuridine [BrdU]+) cell populations, including a radial glial-like (type IIa) cell immunopositive for both S100β and glutamine synthetase (GS). Our data revealed rostrocaudal differences in the density of distinct proliferative populations, and cumulative labeling studies suggested that the cell cycle kinetics of these populations are not uniform between PVZs. Although the peak numbers of differentiated neurons were generated after ~2 weeks among most PVZs, niche-specific decline in the number of newborn neurons in some regions occurred after 4 weeks. Our data suggest that the cytoarchitecture of neurogenic niches and the tempo of neuronal production are regionally distinct in the adult zebrafish forebrain.
    The Journal of Comparative Neurology 02/2012; 520(10):2275-316. · 3.66 Impact Factor
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    ABSTRACT: The gas-filled swimbladder of teleost fishes provides hydrodynamic lift which counteracts the high density of other body tissues, and thereby allows the fish to achieve neutral buoyancy with minimal energy expenditure. In this study, we examined whether the absence of a constant direction gravitational vector affects the ontogeny of the swimbladder and buoyancy control in zebrafish (Danio rerio). We exposed fertilized eggs to simulated microgravity (SMG) in a closed rotating wall vessel with control eggs placed in a similar but nonrotating container. All eggs hatched in both groups. At 96 hr of postfertilization (hpf), all larvae were removed from the experimental and control vessels. At this point, 62% of the control larvae, but only 14% of SMG-exposed larvae, were observed to have inflated their swimbladder. In addition, the mean volume of the inflated swimbladders was significantly greater in the control larvae compared with larvae raised in SMG. After transfer to open stationary observation tanks, larvae with uninflated swimbladders in both groups swam to the surface to complete inflation, but this process was significantly delayed in larvae exposed to SMG. Initial differences in swimbladder inflation and volume between groups disappeared by 144 hpf. Furthermore, there were no apparent changes in patterns of development and maturation of swimbladder musculature, vasculature, or innervation resulting from SMG exposure at later stages of ontogeny. These data indicate that, despite a transient delay in swimbladder inflation in zebrafish larvae exposed to SMG, subsequent swimbladder development in these animals proceeded similarly to that in normal larvae.
    Journal of Experimental Zoology Part A Ecological Genetics and Physiology 03/2011; 315(5):302-13. · 1.61 Impact Factor
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    Benjamin W Lindsey, Frank M Smith, Roger P Croll
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    ABSTRACT: Teleost fishes have body tissues that are denser than water, causing them to sink. Many teleosts therefore possess a gas-filled swimbladder that provides lift, allowing fish to attain neutral buoyancy. The importance of the swimbladder as a buoyancy aid during changing body sizes over ontogeny and its role in determining the swimming depth of fish remain unclear. In this study, we have used the zebrafish (Danio rerio) to investigate changes in the size and shape of the swimbladder during development and examine whether these changes affect the hydrostatic contribution of the swimbladder during swimming. Our results showed that swim-up behavior is critical for larvae to first inflate their swimbladder, decrease body density, and attain neutral buoyancy. Following inflation, we found a strong linear correlation between fish volume and swimbladder volume over ontogeny. This trend was supported by measures of the density of zebrafish, which was conserved within a narrow range between 1.00 +/- 0.001 and 0.996 +/- 0.001 g/cm(3) despite an increase in the swimming depth of zebrafish, which occurred upon transition to a double-chambered organ. Finally, we demonstrated that the contribution of the swimbladder keeps the fish within 1.7% of neutral buoyancy throughout larval development.
    Zebrafish 03/2010; 7(1):85-96. · 2.88 Impact Factor
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    ABSTRACT: Many teleost fishes use a swimbladder, a gas-filled organ in the coelomic cavity, to reduce body density toward neutral buoyancy, thus minimizing the locomotory cost of maintaining a constant depth in the water column. However, for most swimbladder-bearing teleosts, the contribution of this organ to the attainment of neutral buoyancy has not been quantified. Here, we examined the quantitative contribution of the swimbladder to buoyancy and three-dimensional stability in a small cyprinid, the zebrafish (Danio rerio). In aquaria during daylight hours, adult animals were observed at mean depths from 10.1 +/- 6.0 to 14.2 +/- 5.6 cm below the surface. Fish mass and whole-body volume were linearly correlated (r(2) = 0.96) over a wide range of body size (0.16-0.73 g); mean whole-body density was 1.01 +/- 0.09 g cm(-3). Stereological estimations of swimbladder volume from linear dimensions of lateral X-ray images and direct measurements of gas volumes recovered by puncture from the same swimbladders showed that results from these two methods were highly correlated (r(2) = 0.85). The geometric regularity of the swimbladder thus permitted its volume to be accurately estimated from a single lateral image. Mean body density in the absence of the swimbladder was 1.05 +/- 0.04 g cm(-3). The swimbladder occupied 5.1 +/- 1.4% of total body volume, thus reducing whole-body density significantly. The location of the centers of mass and buoyancy along rostro-caudal and dorso-ventral axes overlapped near the ductus communicans, a constriction between the anterior and posterior swimbladder chambers. Our work demonstrates that the swimbladder of the adult zebrafish contributes significantly to buoyancy and attitude stability. Furthermore, we describe and verify a stereological method for estimating swimbladder volume that will aid future studies of the functions of this organ.
    Journal of Morphology 07/2008; 269(6):666-73. · 1.60 Impact Factor
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    ABSTRACT: Directing embryonic stem (ES) cells to differentiate into functional motoneurons has proven to be a strong technique for studying neuronal development as well as being a potential source of tissue for cell replacement therapies involving spinal cord disorders. Unfortunately, one of the mitogenic factors (i.e., sonic hedgehog agonist) used for directed differentiation is not readily available, and thus this technique has not been widely accessible. Here, we present a novel and simple method to derive motoneurons from ES cells using readily attainable reagents. ES cells were derived from a mouse in which enhanced green fluorescent protein (eGFP) was linked to a motoneuron specific promoter. The cells were plated onto a monolayer of 293 EcR-Shh cells that carry an integrated construct for the expression of sonic hedgehog (Shh) under ecdysone-inducible control. To initiate motoneuron differentiation, 293 EcR-Shh:ES cell cocultures were treated with ponasterone A (PA) and retinoic acid for 5 days. PA induces ecdysone, and thus drives Shh expression. To assess differentiation, putative ES cell-derived motoneurons were studied immunocytochemically and cultured on chick myotubes for functional analysis. We found that ES cells differentiated into eGFP+ cells that expressed transcription factors typical of motoneurons. Furthermore, ES cell-derived motoneurons were capable of forming functional connections with muscle fibers in vitro. Finally, when transplanted into the developing chick spinal cord, ES cell-derived motoneurons migrated to the ventral horn and projected axons to appropriate muscle targets. In summary, this simple treatment paradigm produces functional motoneurons that can be used for both developmental and preclinical studies. Disclosure of potential conflicts of interest is found at the end of this article.
    Stem Cells 07/2007; 25(7):1697-706. · 7.70 Impact Factor
  • Benjamin W Lindsey, Vincent Tropepe
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    ABSTRACT: Adult neurogenesis has been identified in all vertebrate species examined thus far. However, an evolutionary trend towards a reduction in both the number of proliferation zones and the overall number of newborn cells has been revealed in more recent lineages of vertebrates, such as mammals. Adult neurogenesis, and in particular the characterization of adult neural stem cells in mammals has been the focus of intense research with the goal of developing new cell-based regenerative treatments for neurodegenerative diseases, spinal cord injury, and acute damage due to stroke. Conversely, most other vertebrate classes, which display widespread production of adult neurons, are not typically used as model systems in this context. A more profound understanding of the structural composition and the mechanisms that support proliferation zones in the mature brain have become critical for revealing how adult neural stem cells are maintained in these regions and how they regulate neurogenesis. In this review we argue that comprehensive analyses of adult neurogenesis in various vertebrate and invertebrate species will lead to a more complete understanding of the fundamental biology and evolution of adult neurogenesis and provide a better framework for testing hypotheses regarding the functional significance of this trait.
    Progress in Neurobiology 01/2007; 80(6):281-307. · 9.04 Impact Factor
  • International Journal of Developmental Neuroscience - INT J DEV NEUROSCI. 01/2006; 24(8):520-520.

Publication Stats

102 Citations
91 Downloads
351 Views
26.49 Total Impact Points

Institutions

  • 2012
    • University of Toronto
      • Department of Cell and Systems Biology
      Toronto, Ontario, Canada
  • 2007–2011
    • Dalhousie University
      • Department of Anatomy and Neurobiology
      Halifax, Nova Scotia, Canada