Smith ScholarWorks - yobetapp,yobet电脑版 Copyright (c) 2021 Smith College All rights reserved. //www.theaslg.com Recent documents in Smith ScholarWorks en-us Fri, 12 Nov 2021 02:29:38 PST 3600 fec16: Data Package for the 2016 United States Federal Elections //www.theaslg.com/dds_data/8 //www.theaslg.com/dds_data/8 Thu, 11 Nov 2021 11:02:03 PST Easily analyze relational data from the United States 2016 federal election cycle as reported by the Federal Election Commission. This package contains data about candidates, committees, and a variety of different financial expenditures. Data is from <https://www.fec.gov/data/browse-data/?tab=bulk-data>.

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Marium Tapal et al.
Who is in charge? : exploring the connection between connexin dependent bioelectrics and morphogen signaling during axis determination in zebrafish //www.theaslg.com/theses/2351 //www.theaslg.com/theses/2351 Thu, 11 Nov 2021 09:46:23 PST Axis determination is a fundamental process that occurs during embryonic development. Differential specification of cell fates across the blastula and gastrula determine where the head, tail, back, and belly will develop. It is readily understood that gradients of biochemical morphogens play a critical signaling role that specify and pattern cell fates during axis determination in the early vertebrate embryo. Such morphogens include members of the Bone Morphogenic Protein (BMP), Fibroblast Growth Factor (FGF), and Nodal families. Their genes are known to be expressed in distinct patterns along the dorsoventral axis in developing zebrafish embryos. Recent evidence suggests that inductive effects of such morphogens may themselves be regulated by different states of membrane potential across tissues. However, no studies to date have examined whether bioelectric signaling regulates the expression and or functions of morphogens in gastrulating embryos. Preliminary studies from our lab suggest that distinct bioelectric patterns may exist prior to the determination of cell fates along the zebrafish axes. To dissect whether bioelectrics may play a superimposing role on the inductive effects of morphogens, we set out to test whether Connexin-mediate bioelectric signaling is essential for early axis determination and whether it operates through FGF signaling. Using a variety of genetic and pharmacological tools to manipulate both connexin and FGF signaling, we show that connexin-mediate bioelectrics is required for proper anterior brain and posterior tail development. Furthermore, we show that proper Fgf8 expression is dependent upon connexin signaling. Our preliminary findings suggest that connexin-dependent bioelectric signaling may regulate FGF expression patterns that have profound impacts on axis determination in zebrafish. Here we propose to take advantage of the high resolution microscopy, and genetic tools of the zebrafish model system to characterize the role that gap junctions play in the differential bioelectric patterns present in the early embryo as well as characterize the nature of bioelectric-mediated morphogenic regulation.

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Janeth Mora-Martinez
H. M. Naqvi’s <i>Home Boy</i> as a Response to Post-9/11 Islamophobia and as Implicit Critique of Mohsin Hamid’s <i>The Reluctant Fundamentalist</i> //www.theaslg.com/eng_facpubs/21 //www.theaslg.com/eng_facpubs/21 Thu, 11 Nov 2021 09:28:00 PST Ambreen Hai Bilattices and the logic of goal modeling //www.theaslg.com/theses/2350 //www.theaslg.com/theses/2350 Thu, 11 Nov 2021 09:27:37 PST Goal modeling is an area of software engineering that allows stakeholders, in domains from software to public planning, to break down their intentions visually and make trade-off decisions. Currently, Grubb et al. are building a web application, BloomingLeaf, that would allow stakeholders to build and to automatically analyze goal models within the Tropos framework. Practical concerns suggest that the best way to allow users to make models large enough to represent most real-world projects is to have them to create smaller submodels that the application automatically merges into a big-picture view. However, the existing merge algorithm is unable to merge information about goal fulfillment in most cases where it differs between submodels.

This project uses the bilattice, a flexible logical formalism introduced by Ginsberg (1986), to propose solutions to the remaining gaps in the model merging algorithm. Bilattices are sets of values with two related orderings, the first ordered by truth vs. falsity (or other dichotomous qualities), and the second by amount of information. The formal syntax BloomingLeaf uses to record the fulfillment of goals is modeled using a nine-element bilattice of hevidence for satisfaction, evidence for deniali pairs. The bilattice structure suggests two uniform approaches to reconcile information from sources that disagree: gullibility (accept everything) and consensus (accept what the sources agree on). The applications portion of this project outlines the results of applying the consensus approach to fulfillment values that differ across models. This strategy produces obvious solutions for most merge cases, and a few promising solutions for the remaining cases.

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Isabel Grace Montesanto
Historicizing Coming out : a cinematic encounter between national heterosexuality and gay identity in East Germany //www.theaslg.com/theses/2349 //www.theaslg.com/theses/2349 Thu, 11 Nov 2021 08:48:56 PST Madeline Grace Michels Righting/Writing the Black Female Body in Contemporary Afro-Brazilian Literature //www.theaslg.com/afr_books/3 //www.theaslg.com/afr_books/3 Thu, 11 Nov 2021 06:54:37 PST Flávia Santos de Araújo Master of Poisons //www.theaslg.com/afr_books/2 //www.theaslg.com/afr_books/2 Thu, 11 Nov 2021 06:54:35 PST Award-winning author Andrea Hairston weaves together African folktales and postcolonial literature into unforgettable fantasy in Master of Poisons.

The world is changing. Poison desert eats good farmland. Once-sweet water turns foul. The wind blows sand and sadness across the Empire. To get caught in a storm is death. To live and do nothing is death. There is magic in the world, but good conjure is hard to find.

Djola, righthand man and spymaster of the lord of the Arkhysian Empire, is desperately trying to save his adopted homeland, even in exile.

Awa, a young woman training to be a powerful griot, tests the limits of her knowledge and comes into her own in a world of sorcery, floating cities, kindly beasts, and uncertain men.

Awash in the rhythms of folklore and storytelling and rich with Hairston's characteristic lush prose, Master of Poisons is epic fantasy that will bleed your mind with its turns of phrase and leave you aching for the world it burns into being. (From the publisher.)

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Andrea Hairston
Observation of Quantum Oscillations in The Low Temperature Specific Heat of SmB<sub>6</sub> //www.theaslg.com/phy_facpubs/78 //www.theaslg.com/phy_facpubs/78 Tue, 09 Nov 2021 08:43:38 PST We report measurements of the low-temperature specific heat of Al-flux-grown samples of SmB6 in magnetic fields up to 32 T. Quantum oscillations periodic in \emph{1/H} are observed between 8 and 32 T at selected angles between [001] and [111]. The observed frequencies and their angular dependence are consistent with previous magnetic torque measurements of SmB6 but the effective masses inferred from Lifshitz-Kosevich theory are significantly larger and closer to those inferred from zero-field specific heat. Our results are thus consistent with a bulk density of states origin for the previously observed quantum oscillations.

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Patrick G. LaBarre et al.
The Law of Nature in Locke's Second Treatise: Is Locke a Hobbesian? //www.theaslg.com/gov_facpubs/36 //www.theaslg.com/gov_facpubs/36 Tue, 09 Nov 2021 08:29:26 PST The question addressed by this essay is whether Thomas Hobbes is the true intellectual forebear of John Locke. A brief comparison of the teachings of these two authors with respect to natural justice and civil justice would seem to suggest that Locke is a determined adversary of Hobbes whose views on justice are reducible to the maxim that "might makes right." But a re-examination of Locke's Second Treatise shows that Locke adopts this principle with hardly less thoroughness than Hobbes. Even so, an important difference remains, for Locke takes steps to disguise the grim reality of power, whereas Hobbes makes the enlightenment of people the sine qua non of his political science. Locke's departure from Hobbes is seen as an attempt to instill in the body politic a degree of justice that would not otherwise exist.

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John Patrick Coby
Aristotle' s Three Cities and the Problem of Faction //www.theaslg.com/gov_facpubs/35 //www.theaslg.com/gov_facpubs/35 Tue, 09 Nov 2021 08:29:23 PST Aristotle describes the polis as a self-sufficient compound. Its regime, he says, is responsible for shaping the whole character of the city' s people. But rarely is the city unified in its parts, and the formative power of the regime is not always this extensive. There are in fact three kinds of cities depicted in the Politics. They differ by the degree of partnership tying city members together. Accordingly, the problem of faction and its cure differs for each: for some cities, where the regime is unitary, the cure is consent; for others, with mixed regimes, it is participation; but for the ideal city it is homogeneity.

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John Patrick Coby
Distinct Mechanisms Regulate Slow-Muscle Development //www.theaslg.com/bio_facpubs/207 //www.theaslg.com/bio_facpubs/207 Mon, 08 Nov 2021 07:31:54 PST Vertebrate muscle development begins with the patterning of the paraxial mesoderm by inductive signals from midline tissues [1, 2]. Subsequent myotome growth occurs by the addition of new muscle fibers. We show that in zebrafish new slow-muscle fibers are first added at the end of the segmentation period in growth zones near the dorsal and ventral extremes of the myotome, and this muscle growth continues into larval life. In marine teleosts, this mechanism of growth has been termed stratified hyperplasia [3]. We have tested whether these added fibers require an embryonic architecture of muscle fibers to support their development and whether their fate is regulated by the same mechanisms that regulate embryonic muscle fates. Although Hedgehog signaling is required for the specification of adaxial-derived slow-muscle fibers in the embryo [4, 5], we show that in the absence of Hh signaling, stratified hyperplastic growth of slow muscle occurs at the correct time and place, despite the complete absence of embryonic slow-muscle fibers to serve as a scaffold for addition of these new slow-muscle fibers. We conclude that slow-muscle-stratified hyperplasia begins after the segmentation period during embryonic development and continues during the larval period. Furthermore, the mechanisms specifying the identity of these new slow-muscle fibers are different from those specifying the identity of adaxial-derived embryonic slow-muscle fibers. We propose that the independence of early, embryonic patterning mechanisms from later patterning mechanisms may be necessary for growth.

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Michael J.F. Barresi et al.
Somite Development in Zebrafish //www.theaslg.com/bio_facpubs/208 //www.theaslg.com/bio_facpubs/208 Mon, 08 Nov 2021 07:31:54 PST A full understanding of somite development requires knowledge of the molecular genetic pathways for cell determination as well as the cellular behaviors that underlie segmentation, somite epithelialization, and somite patterning. The zebrafish has long been recognized as an ideal organism for cellular and histological studies of somite patterning. In recent years, genetics has proven to be a very powerful complementary approach to these embryological studies, as genetic screens for zebrafish mutants defective in somitogenesis have identified over 50 genes that are necessary for normal somite development. Zebrafish is thus an ideal system in which to analyze the role of specific gene products in regulating the cell behaviors that underlie somite development. We review what is currently known about zebrafish somite development and compare it where appropriate to somite development in chick and mouse. We discuss the processes of segmentation and somite epithelialization, and then review the patterning of cell types within the somite. We show directly, for the first time, that muscle cell and sclerotome migrations occur at the same time. We end with a look at the many questions about somitogenesis that are still unanswered.

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Heather L. Stickney et al.
Multiple Roles for Hedgehog Signaling in Zebrafish Pituitary Development //www.theaslg.com/bio_facpubs/205 //www.theaslg.com/bio_facpubs/205 Mon, 08 Nov 2021 07:31:53 PST The endocrine-secreting lobe of the pituitary gland, or adenohypophysis, forms from cells at the anterior margin of the neural plate through inductive interactions involving secreted morphogens of the Hedgehog (Hh), fibroblast growth factor (FGF), and bone morphogenetic protein (BMP) families. To better understand when and where Hh signaling influences pituitary development, we have analyzed the effects of blocking Hh signaling both pharmacologically (cyclopamine treatments) and genetically (zebrafish Hh pathway mutants). While current models state that Shh signaling from the oral ectoderm patterns the pituitary after placode induction, our data suggest that Shh plays a direct early role in both pituitary induction and patterning, and that early Hh signals comes from adjacent neural ectoderm. We report that Hh signaling is necessary between 10 and 15 h of development for induction of the zebrafish adenohypophysis, a time when shh is expressed only in neural tissue. We show that the Hh responsive genes ptc1 and nk2.2 are expressed in preplacodal cells at the anterior margin of the neural tube at this time, indicating that these cells are directly receiving Hh signals. Later (15-20 h) cyclopamine treatments disrupt anterior expression of nk2.2 and Prolactin, showing that early functional patterning requires Hh signals. Consistent with a direct role for Hh signaling in pituitary induction and patterning, overexpression of Shh results in expanded adenohypophyseal expression of lim3, expansion of nk2.2 into the posterior adenohypophysis, and an increase in Prolactin- and Somatolactin-secreting cells. We also use the zebrafish Hh pathway mutants to document the range of pituitary defects that occur when different elements of the Hh signaling pathway are mutated. These defects, ranging from a complete loss of the adenohypophysis (smu/smo and yot/gli2 mutants) to more subtle patterning defects (dtr/gli1 mutants), may correlate to human Hh signaling mutant phenotypes seen in Holoprosencephaly and other congenital disorders. Our results reveal multiple and distinct roles for Hh signaling in the formation of the vertebrate pituitary gland, and suggest that Hh signaling from neural ectoderm is necessary for induction and functional patterning of the vertebrate pituitary gland.

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Jennifer L. Sbrogna et al.
Functional Morphology and Developmental Biology of Zebrafish: Reciprocal Illumination from an Unlikely Couple //www.theaslg.com/bio_facpubs/206 //www.theaslg.com/bio_facpubs/206 Mon, 08 Nov 2021 07:31:53 PST Functional morphology has benefited greatly from the input of techniques and thinking from other disciplines. This has been especially productive in situations where each discipline has made significant contributions to a particular research topic. A combination of methodologies from functional morphology and developmental biology has allowed us to characterize feeding mechanics of first-feeding larval zebrafish (Danio rerio). Contrary to kinematic patterns commonly seen in adult teleosts, larval zebrafish showed no lateral abduction during the expansive phase of a suction-feeding event. Instead, dorsoventral expansion of the buccal chamber, more typical of patterns seen in primitive fishes, characterized the expansive phase. Moreover, a pronounced preparatory phase during which the buccal chamber is constricted by the protractor hyoideus was consistently seen in first-feeding larval kinematics. Key kinematic variables associated with first feeding correlated significantly with the hydrodynamic regime as measured by the Reynolds number. Using the tools of both functional morphology and developmental biology we have not only determined which cranial muscles are important for successful feeding but also uncovered important physiological differences in muscle structure. Muscles necessary for the rapid dorsoventral expansion of the head are composed primarily of fast-twitch fibers while those involved in more tonic contractions such as hyoid protraction have more slow-twitch muscle fibers. While most evolutionary developmental studies have examined mechanisms responsible for large evolutionary changes in morphology, we propose that the type of data uncovered in functional studies can lead to the generation of hypotheses concerning the developmental mechanisms responsible for smaller intra- and/or interspecific changes.

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L. Patricia Hernández et al.
Hedgehog Regulated Slit Expression Determines Commissure and Glial Cell Position in the Zebrafish Forebrain //www.theaslg.com/bio_facpubs/204 //www.theaslg.com/bio_facpubs/204 Mon, 08 Nov 2021 07:31:52 PST Three major axon pathways cross the midline of the vertebrate forebrain early in embryonic development: the postoptic commissure (POC), the anterior commissure (AC) and the optic nerve. We show that a small population of Gfap+ astroglia spans the midline of the zebrafish forebrain in the position of, and prior to, commissural and retinal axon crossing. These glial 'bridges' form in regions devoid of the guidance molecules slit2 and slit3, although a subset of these glial cells express slit1a. We show that Hh signaling is required for commissure formation, glial bridge formation, and the restricted expression of the guidance molecules slit1a, slit2, slit3 and sema3d, but that Hh does not appear to play a direct role in commissural and retinal axon guidance. Reducing Slit2 and/or Slit3 function expanded the glial bridges and caused defasciculation of the POC, consistent with a 'channeling' role for these repellent molecules. By contrast, reducing Slit1a function led to reduced midline axon crossing, suggesting a distinct role for Slit1a in midline axon guidance. Blocking Slit2 and Slit3, but not Slit1a, function in the Hh pathway mutant yot (gli2DR) dramatically rescued POC axon crossing and glial bridge formation at the midline, indicating that expanded Slit2 and Slit3 repellent function is largely responsible for the lack of midline crossing in these mutants. This analysis shows that Hh signaling helps to pattern the expression of Slit guidance molecules that then help to regulate glial cell position and axon guidance across the midline of the forebrain.

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Michael J.F. Barresi et al.
Generality of Vertebrate Developmental Patterns: Evidence for a Dermomyotome in Fish //www.theaslg.com/bio_facpubs/203 //www.theaslg.com/bio_facpubs/203 Mon, 08 Nov 2021 07:31:51 PST The somitic compartment that gives rise to trunk muscle and dermis in amniotes is an epithelial sheet on the external surface of the somite, and is known as the dermomyotome. However, despite its central role in the development of the trunk and limbs, the evolutionary history of the dermomyotome and its role in nonamniotes is poorly understood. We have tested whether a tissue with the morphological and molecular characteristics of a dermomyotome exists in nonamniotes. We show that representatives of the agnathans and of all major clades of gnathostomes each have a layer of cells on the surface of the somite, external to the embryonic myotome. These external cells do not show any signs of terminal myogenic or dermogenic differentiation. Moreover, in the embryos of bony fishes as diverse as sturgeons (Chondrostei) and zebrafish (Teleostei) this layer of cells expresses the pax3 and pax7 genes that mark myogenic precursors. Some of the pax7-expressing cells also express the differentiation-promoting myogenic regulatory factor Myogenin and appear to enter into the myotome. We therefore suggest that the dermomyotome is an ancient and conserved structure that evolved prior to the last common ancestor of all vertebrates. The identification of a dermomyotome in fish makes it possible to apply the powerful cellular and genetic approaches available in zebrafish to the understanding of this key developmental structure.

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S. H. Devoto et al.
Essential Genes for Astroglial Development and Axon Pathfinding During Zebrafish Embryogenesis //www.theaslg.com/bio_facpubs/201 //www.theaslg.com/bio_facpubs/201 Mon, 08 Nov 2021 07:31:50 PST The formation of the central nervous system depends on the coordinated development of neural and glial cell types that arise from a common precursor. Using an existing group of zebrafish mutants generated by viral insertion, we performed a "shelf-screen" to identify genes necessary for astroglial development and axon scaffold formation. We screened 274 of 315 viral insertion lines using antibodies that label axons (anti-Acetylated Tubulin) and astroglia (anti-Gfap) and identified 25 mutants with defects in gliogenesis, glial patterning, neurogenesis, and axon guidance. We also identified a novel class of mutants affecting radial glial cell numbers. Defects in astroglial patterning were always associated with axon defects, supporting an important role for axon-glial interactions during axon scaffold development. The genes disrupted in these viral lines have all been identified, providing a powerful new resource for the study of axon guidance, glio- and neurogenesis, and neuron-glial interactions during development of the vertebrate CNS.

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Michael J.F. Barresi et al.
Tissue Targeted Embryonic Chimeras: Zebrafish Gastrula Cell Transplantation //www.theaslg.com/bio_facpubs/202 //www.theaslg.com/bio_facpubs/202 Mon, 08 Nov 2021 07:31:50 PST Certain fundamental questions in the field of developmental biology can only be answered when cells are placed in novel environments or when small groups of cells in a larger context are altered. Watching how one cell interacts with and behaves in a unique environment is essential to characterizing cell functions. Determining how the localized misexpression of a specific protein influences surrounding cells provides insightful information on the roles that protein plays in a variety of developmental processes. Our lab uses the zebrafish model system to uniquely combine genetic approaches with classical transplantation techniques to generate genotypic or phenotypic chimeras. We study neuron-glial cell interactions during the formation of forebrain commissures in zebrafish. This video describes a method that allows our lab to investigate the role of astroglial populations in the diencephalon and the roles of specific guidance cues that influence projecting axons as they cross the midline. Due to their transparency zebrafish embryos are ideal models for this type of ectopic cell placement or localized gene misexpression. Tracking transplanted cells can be accomplished using a vital dye or a transgenic fish line expressing a fluorescent protein. We demonstrate here how to prepare donor embryos with a vital dye tracer for transplantation, as well as how to extract and transplant cells from one gastrula staged embryo to another. We present data showing ectopic GFP+ transgenic cells within the forebrain of zebrafish embryos and characterize the location of these cells with respect to forebrain commissures. In addition, we show laser scanning confocal timelapse microscopy of Alexa 594 labeled cells transplanted into a GFP+ transgenic host embryo. These data provide evidence that gastrula staged transplantation enables the targeted positioning of ectopic cells to address a variety of questions in Developmental Biology.

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Elizabeth R. Deschene et al.
Vincristine and Bortezomib Cause Axon Outgrowth and Behavioral Defects in Larval Zebrafish //www.theaslg.com/bio_facpubs/200 //www.theaslg.com/bio_facpubs/200 Mon, 08 Nov 2021 07:31:49 PST Peripheral neuropathy is a common side effect of a number of pharmaceutical compounds, including several chemotherapy drugs. Among these are vincristine sulfate, a mitotic inhibitor used to treat a variety of leukemias, lymphomas, and other cancers, and bortezomib, a 26S proteasome inhibitor used primarily to treat relapsed multiple myeloma and mantle cell lymphoma. To gain insight into the mechanisms by which these compounds act, we tested their effects in zebrafish. Vincristine or bortezomib given during late embryonic development caused significant defects at both behavioral and cellular levels. Intriguingly, the effects of the two drugs appear to be distinct. Vincristine causes uncoordinated swimming behavior, which is coupled with a reduction in the density of sensory innervation and overall size of motor axon arbors. Bortezomib, in contrast, increases the duration and amplitude of muscle contractions associated with escape swimming, which is coupled with a preferential reduction in fine processes and branches of sensory and motor axons. These results demonstrate that zebrafish is a convenient in vivo assay system for screening potential pharmaceutical compounds for neurotoxic side effects, and they provide an important step toward understanding how vincristine and bortezomib cause peripheral neuropathy.

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Tahsin M. Khan et al.
Kif11 Dependent Cell Cycle Progression in Radial Glial Cells is Required for Proper Neurogenesis in the Zebrafish Neural Tube //www.theaslg.com/bio_facpubs/198 //www.theaslg.com/bio_facpubs/198 Mon, 08 Nov 2021 07:31:48 PST Radial glia serve as the resident neural stem cells in the embryonic vertebrate nervous system, and their proliferation must be tightly regulated to generate the correct number of neuronal and glial cell progeny in the neural tube. During a forward genetic screen, we recently identified a zebrafish mutant in the kif11 loci that displayed a significant increase in radial glial cell bodies at the ventricular zone of the spinal cord. Kif11, also known as Eg5, is a kinesin-related, plus-end directed motor protein responsible for stabilizing and separating the bipolar mitotic spindle. We show here that Gfap+ radial glial cells express kif11 in the ventricular zone and floor plate. Loss of Kif11 by mutation or pharmacological inhibition with S-trityl l-cysteine (STLC) results in monoastral spindle formation in radial glial cells, which is characteristic of mitotic arrest. We show that M-phase radial glia accumulate over time at the ventricular zone in kif11 mutants and STLC treated embryos. Mathematical modeling of the radial glial accumulation in kif11 mutants not only confirmed an ~226× delay in mitotic exit (likely a mitotic arrest), but also predicted two modes of increased cell death. These modeling predictions were supported by an increase in the apoptosis marker, anti-activated Caspase-3, which was also found to be inversely proportional to a decrease in cell proliferation. In addition, treatment with STLC at different stages of neural development uncovered two critical periods that most significantly require Kif11 function for stem cell progression through mitosis. We also show that loss of Kif11 function causes specific reductions in oligodendroglia and secondary interneurons and motorneurons, suggesting these later born populations require proper radial glia division. Despite these alterations to cell cycle dynamics, survival, and neurogenesis, we document unchanged cell densities within the neural tube in kif11 mutants, suggesting that a mechanism of compensatory regulation may exist to maintain overall proportions in the neural tube. We propose a model in which Kif11 normally functions during mitotic spindle formation to facilitate the progression of radial glia through mitosis, which leads to the maturation of progeny into specific secondary neuronal and glial lineages in the developing neural tube.

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Kimberly Johnson et al.
Macondo Crude Oil from the Deepwater Horizon Oil Spill Disrupts Specific Developmental Processes During Zebrafish Embryogenesis //www.theaslg.com/bio_facpubs/199 //www.theaslg.com/bio_facpubs/199 Mon, 08 Nov 2021 07:31:48 PST Background: The Deepwater Horizon disaster was the largest marine oil spill in history, and total vertical exposure of oil to the water column suggests it could impact an enormous diversity of ecosystems. The most vulnerable organisms are those encountering these pollutants during their early life stages. Water-soluble components of crude oil and specific polycyclic aromatic hydrocarbons have been shown to cause defects in cardiovascular and craniofacial development in a variety of teleost species, but the developmental origins of these defects have yet to be determined. We have adopted zebrafish, Danio rerio, as a model to test whether water accumulated fractions (WAF) of the Deepwater Horizon oil could impact specific embryonic developmental processes. While not a native species to the Gulf waters, the developmental biology of zebrafish has been well characterized and makes it a powerful model system to reveal the cellular and molecular mechanisms behind Macondo crude toxicity.

Results: WAF of Macondo crude oil sampled during the oil spill was used to treat zebrafish throughout embryonic and larval development. Our results indicate that the Macondo crude oil causes a variety of significant defects in zebrafish embryogenesis, but these defects have specific developmental origins. WAF treatments caused defects in craniofacial development and circulatory function similar to previous reports, but we extend these results to show they are likely derived from an earlier defect in neural crest cell development. Moreover, we demonstrate that exposure to WAFs causes a variety of novel deformations in specific developmental processes, including programmed cell death, locomotor behavior, sensory and motor axon pathfinding, somitogenesis and muscle patterning. Interestingly, the severity of cell death and muscle phenotypes decreased over several months of repeated analysis, which was correlated with a rapid drop-off in the aromatic and alkane hydrocarbon components of the oil.

Conclusions: Whether these teratogenic effects are unique to the oil from the Deepwater Horizon oil spill or generalizable for most crude oil types remains to be determined. This work establishes a model for further investigation into the molecular mechanisms behind crude oil mediated deformations. In addition, due to the high conservation of genetic and cellular processes between zebrafish and other vertebrates, our work also provides a platform for more focused assessment of the impact that the Deepwater Horizon oil spill has had on the early life stages of native fish species in the Gulf of Mexico and the Atlantic Ocean.

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T. Yvanka de Soysa et al.
Estrogens Suppress a Behavioral Phenotype in Zebrafish Mutants of the Autism Risk Gene, CNTNAP2 //www.theaslg.com/bio_facpubs/197 //www.theaslg.com/bio_facpubs/197 Mon, 08 Nov 2021 07:31:47 PST Autism spectrum disorders (ASDs) are a group of devastating neurodevelopmental syndromes that affect up to 1 in 68 children. Despite advances in the identification of ASD risk genes, the mechanisms underlying ASDs remain unknown. Homozygous loss-of-function mutations in Contactin Associated Protein-like 2 (CNTNAP2) are strongly linked to ASDs. Here we investigate the function of Cntnap2 and undertake pharmacological screens to identify phenotypic suppressors. We find that zebrafish cntnap2 mutants display GABAergic deficits, particularly in the forebrain, and sensitivity to drug-induced seizures. High-throughput behavioral profiling identifies nighttime hyperactivity in cntnap2 mutants, while pharmacological testing reveals dysregulation of GABAergic and glutamatergic systems. Finally, we find that estrogen receptor agonists elicit a behavioral fingerprint anti-correlative to that of cntnap2 mutants and show that the phytoestrogen biochanin A specifically reverses the mutant behavioral phenotype. These results identify estrogenic compounds as phenotypic suppressors and illuminate novel pharmacological pathways with relevance to autism. Hoffman et al. use zebrafish mutants of the autism risk gene Contactin Associated Protein-like 2 (CNTNAP2) to conduct high-throughput quantitative behavioral profiling and pharmacological screening. This approach reveals dysregulation of GABAergic and glutamatergic systems in mutants and identifies estrogenic compounds as suppressors of the mutant behavioral phenotype.

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Ellen J. Hoffman et al.
Radial Glia Inhibit Peripheral Glial Infiltration into the Spinal Cord at Motor Exit Point Transition Zones //www.theaslg.com/bio_facpubs/196 //www.theaslg.com/bio_facpubs/196 Mon, 08 Nov 2021 07:31:46 PST In the mature vertebrate nervous system, central and peripheral nervous system (CNS and PNS, respectively) GLIA myelinate distinct motor axon domains at the motor exit point transition zone (MEP TZ). How these cells preferentially associate with and myelinate discrete, non-overlapping CNS versus PNS axonal segments, is unknown. Using in vivo imaging and genetic cell ablation in zebrafish, we demonstrate that radial glia restrict migration of PNS glia into the spinal cord during development. Prior to development of radial glial endfeet, peripheral cells freely migrate back and forth across the MEP TZ. However, upon maturation, peripherally located cells never enter the CNS. When we ablate radial glia, peripheral glia ectopically migrate into the spinal cord during developmental stages when they would normally be restricted. These findings demonstrate that radial glia contribute to both CNS and PNS development and control the unidirectional movement of glial cell types across the MEP TZ early in development.

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Cody J. Smith et al.
Gfap-Positive Radial Glial Cells are an Essential Progenitor Population for Later-Born Neurons and Glia in the Zebrafish Spinal Cord //www.theaslg.com/bio_facpubs/195 //www.theaslg.com/bio_facpubs/195 Mon, 08 Nov 2021 07:31:45 PST Radial glial cells are presumptive neural stem cells (NSCs) in the developing nervous system. The direct requirement of radial glia for the generation of a diverse array of neuronal and glial subtypes, however, has not been tested. We employed two novel transgenic zebrafish lines and endogenous markers of NSCs and radial glia to show for the first time that radial glia are essential for neurogenesis during development. By using the gfap promoter to drive expression of nuclear localized mCherry we discerned two distinct radial glial-derived cell types: a major nestin+/Sox2+ subtype with strong gfap promoter activity and a minor Sox2+ subtype lacking this activity. Fate mapping studies in this line indicate that gfap+ radial glia generate later-born CoSA interneurons, secondary motorneurons, and oligodendroglia. In another transgenic line using the gfap promoter-driven expression of the nitroreductase enzyme, we induced cell autonomous ablation of gfap+ radial glia and observed a reduction in their specific derived lineages, but not Blbp+ and Sox2+/gfap-negative NSCs, which were retained and expanded at later larval stages. Moreover, we provide evidence supporting classical roles of radial glial in axon patterning, blood-brain barrier formation, and locomotion. Our results suggest that gfap+ radial glia represent the major NSC during late neurogenesis for specific lineages, and possess diverse roles to sustain the structure and function of the spinal cord. These new tools will both corroborate the predicted roles of astroglia and reveal novel roles related to development, physiology, and regeneration in the vertebrate nervous system.

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Kimberly Johnson et al.
Engaging New Audiences with Imaging and Mcroscopy //www.theaslg.com/bio_facpubs/194 //www.theaslg.com/bio_facpubs/194 Mon, 08 Nov 2021 07:31:44 PST In this Spotlight, we hear first-hand accounts from five scientists and educators who use microscopy and imaging to engage, entertain, educate and inspire new audiences with science and the field of developmental biology in particular. The 'voices' that follow each convey each authors' own personal take on why microscopy is such a powerful tool for capturing the minds, and the hearts, of scientists, students and the public alike. They discuss how microscopy and imaging can reveal new worlds, and improve our communication and understanding of developmental biology, as well as break down barriers and promote diversity for future generations of scientific researchers.

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Michael J. Barresi et al.