Biology Commons^™

The Role Of Climate In The Dynamics Of Annual Plants In A Chihuahuan Desert Ecosystem, Danielle Ignace, Nancy Huntly, Peter Chesson

Biological Sciences: Faculty Publications

Question: What is the role of temporal climate fluctuations in the dynamics of desert winter annual plants in the Portal Bajada, and in the sustained irruption of the non-native annual plant species, Erodium cicutarium?

Field site: Portal Bajada, San Simon Valley, Arizona, USA. Methods: We counted plants at flowering over a 21-year period on twelve permanent plots and related these numbers to weather data collected at an on-site weather station, supplemented by observations from the National Climate Data Center. Specific summary climate variables considered most relevant to annual plant biology were developed as candidate predictors of plant response variables.

Statistical …

Intraspecific Differences In Molecular Stress Responses And Coral Pathobiome Contribute To Mortality Under Bacterial Challenge In Acropora Millepora, Rachel M. Wright, Carly D. Kenkel, Carly E. Dunn, Erin N. Shilling, Line K. Bay, Mikhail V. Matz

Biological Sciences: Faculty Publications

Disease causes significant coral mortality worldwide; however, factors responsible for intraspecific variation in disease resistance remain unclear. We exposed fragments of eight Acropora millepora colonies (genotypes) to putatively pathogenic bacteria (Vibrio spp.). Genotypes varied from zero to >90% mortality, with bacterial challenge increasing average mortality rates 4-6 fold and shifting the microbiome in favor of stress-associated taxa. Constitutive immunity and subsequent immune and transcriptomic responses to the challenge were more prominent in high-mortality individuals, whereas low-mortality corals remained largely unaffected and maintained expression signatures of a healthier condition (i.e., did not launch a large stress response). Our results suggest that …

Distribution Of Abundant And Active Planktonic Ciliates In Coastal And Slope Waters Off New England, Sarah J. Tucker, George B. Mcmanus, Laura A. Katz, Jean-David Grattepanche

Biological Sciences: Faculty Publications

Despite their important role of linking microbial and classic marine food webs, data on biogeographical patterns of microbial eukaryotic grazers are limited, and even fewer studies have used molecular tools to assess active (i.e., those expressing genes) community members. Marine ciliate diversity is believed to be greatest at the chlorophyll maximum, where there is an abundance of autotrophic prey, and is often assumed to decline with depth. Here, we assess the abundant (DNA) and active (RNA) marine ciliate communities throughout the water column at two stations off the New England coast (Northwest Atlantic)—a coastal station 43 km from shore (40 …

Insights Into Transgenerational Epigenetics From Studies Of Ciliates, Olivia A. Pilling, Anna J. Rogers, Bethaney Gulla-Devaney, Laura A. Katz

Biological Sciences: Faculty Publications

Epigenetics, a term with many meanings, can be broadly defined as the study of dynamic states of the genome. Ciliates, a clade of unicellular eukaryotes, can teach us about the intersection of epigenetics and evolution due to the advantages of working with cultivable ciliate lineages, plus their tendency to express extreme phenotypes such as heritable doublet morphology. Moreover, ciliates provide a powerful model for studying epigenetics given the presence of dimorphic nuclei – a somatic macronucleus and germline micronucleus – within each cell. Here, we exemplify the power of studying ciliates to learn about epigenetic phenomena. We highlight “classical” examples …

Unusual Features Of Non-Dividing Somatic Macronuclei In The Ciliate Class Karyorelictea, Ying Yan, Anna J. Rogers, Feng Gao, Laura A. Katz

Biological Sciences: Faculty Publications

Genome structure and nuclear organization have been intensely studied in model ciliates such as Tetrahymena and Paramecium, yet few studies have focused on nuclear features of other ciliate clades including the class Karyorelictea. In most ciliates, both the somatic macronuclei and germline micronuclei divide during cell division and macronuclear development only occurs after conjugation. However, the macronuclei of Karyorelictea are non-dividing (i.e. division minus (Div−)) and develop anew from micronuclei during each asexual division. As macronuclei age within Karyorelictea, they undergo changes in morphology and DNA content until they are eventually degraded and replaced by newly developed macronuclei. No less …

Pteronura Brasiliensis (Carnivora: Mustelidae), Paula Noonan, Siobhan Prout, Virginia Hayssen

Biological Sciences: Faculty Publications

Pteronura brasiliensis (Zimmermann, 1780), the giant otter, is the largest freshwater otter. Found in South America, it inhabits slow-moving rivers and creeks and feeds predominantly on fish. Extinct in the southern portions of its former range, P. brasiliensis is listed as "Endangered" by the International Union for Conservation of Nature and Natural Resources. Threats to P. brasiliensis include habitat destruction, illegal hunting, and disease.

A Dna Origami Platform For Quantifying Protein Copy Number In Super-Resolution, Francesca Cella Zanacchi, Carlo Manzo, Angel S. Alvarez, Nathan D. Derr, Maria F. Garcia-Parajo, Melike Lakadamyali

Biological Sciences: Faculty Publications

Single-molecule-based super-resolution microscopy offers researchers a unique opportunity to quantify protein copy number with nanoscale resolution. However, while fluorescent proteins have been characterized for quantitative imaging using calibration standards, similar calibration tools for immunofluorescence with small organic fluorophores are lacking. Here we show that DNA origami, in combination with GFP antibodies, is a versatile platform for calibrating fluorophore and antibody labeling efficiency to quantify protein copy number in cellular contexts using super-resolution microscopy.

Disentangling Sources Of Variation In Ssu Rdna Sequences From Single Cell Analyses Of Ciliates: Impact Of Copy Number Variation And Experimental Error, Chundi Wang, Tengteng Zhang, Yurui Wang, Laura A. Katz, Feng Gao, Weibo Song

Biological Sciences: Faculty Publications

Small subunit ribosomal DNA (SSU rDNA) is widely used for phylogenetic inference, barcoding and other taxonomy-based analyses. Recent studies indicate that SSU rDNA of ciliates may have a high level of sequence variation within a single cell, which impacts the interpretation of rDNA-based surveys. However, sequence variation can come from a variety of sources including experimental errors, especially the mutations generated by DNA polymerase in PCR. In the present study, we explore the impact of four DNA polymerases on sequence variation and find that low-fidelity polymerases exaggerate the estimates of single-cell sequence variation. Therefore, using a polymerase with high fidelity …

A Novel, Species-Specific, Real-Time Pcr Assay For The Detection Of The Emerging Zoonotic Parasite Ancylostoma Ceylanicum In Human Stool, Marina Papaiakovou, Nils Pilotte, Jessica R. Grant, Rebecca J. Traub, Stacey Llewellyn, James S. Mccarthy, Alejandro J. Krolewiecki, Rubén Cimino, Rojelio Mejia, Steven A. Williams

Biological Sciences: Faculty Publications

Historically, Ancylostoma ceylanicum has been viewed as an uncommon cause of human hookworm infection, with minimal public health importance. However, recent reports have indicated that this zoonotic hookworm causes a much greater incidence of infection within certain human populations than was previously believed. Current methods for the species-level detection of A. ceylanicum rely on techniques that involve conventional PCR accompanied by restriction enzyme digestions. These PCR-based assays are not only labo- rious but they lack sensitivity as they target suboptimal regions on the DNA. As efforts aimed at the eradication of hookworm disease have grown substantially over the last decade, …

Callosciurus Prevostii (Rodentia: Sciuridae), Peter W.W. Lurz, Isabella Fielding, Virginia Hayssen

Biological Sciences: Faculty Publications

Prevost's squirrel, Callosciurus prevostii (Desmarest, 1822), is a diurnal, medium-sized, arboreal squirrel. Its distribution extends from peninsular Thailand and Sumatra to northern Sulawesi, Borneo, and adjacent islands. It inhabits secondary forests, fruit orchards, as well as palm and coconut plantations. Fruit is the main component of its diet, but some arthropods are also eaten. The International Union for Conservation of Nature and Natural Resources lists C. prevostii as "Least Concern" due to its wide distribution and tolerance for some degree of habitat modification.

Application Of A Household-Based Molecular Xenomonitoring Strategy To Evaluate The Lymphatic Filariasis Elimination Program In Tamil Nadu, India, Swaminathan Subramanian, Purushothaman Jambulingam, Brian K. Chu, Candasamy Sadanandane, Venkatesan Vasuki, Adinarayanan Srividya, Mohamed S. Mohideen Abdulkader, Kaliannagounder Krishnamoorthy, Harikishan K. Raju, Sandra J. Laney, Steven A. Williams, Ralph H. Henderson

Biological Sciences: Faculty Publications

Lymphatic filariasis (LF) is one of the world’s foremost debilitating infectious diseases with nearly 800 million people at risk of infection. Given that LF is a mosquito-borne disease, the use of molecular xenomonitoring (MX) to detect parasite DNA/RNA in mosquitoes can serve as a valuable tool for LF monitoring and evaluation, particularly in Culexvector areas. We investigated using MX in a low-level prevalence district of Tamil Nadu, India by applying a household-based sampling strategy to determine trap location sites. Two independent mosquito samples were collected in each of a higher human infection hotspot area (sites with community microfilaria prevalence �1%) …

A Program Aimed Toward Inclusive Excellence For Underrepresented Undergraduate Women In The Sciences, Laura A. Katz, Kathryn M. Aloisio, Nicholas J. Horton, Minh Ly, Sara B. Pruss, Kate Queeney, Cate Rowen, Patricia Marten Dibartolo

Biological Sciences: Faculty Publications

Created to foster inclusive excellence, Smith College’s Achieving Excellence in Mathematics, Engineering, and Science (AEMES) Scholars program provides early faculty-mentored research opportunities and other programming as a way to foster success in academic outcomes for underrepresented women in science. Using academic record data, we compared Scholars’ outcomes over time with those of underrepresented students before program launch and to relevant peer comparison groups. Since its launch, AEMES Scholars have achieved significantly higher gateway life sciences course grade point averages (GPAs), rates of persistence in life and natural sciences, and participation in natural sciences advanced research relative to baseline. Gains for …

Differential Toxic Effects Of Ulva Lactuca (Chlorophyta) On The Herbivorous Gastropods, Littorina Littorea And L. Obtusata (Mollusca), Paulette Peckol, Alysha B. Putnam

Biological Sciences: Faculty Publications

Members of the genus Ulva are widespread and abundant in intertidal and shallow subtidal areas but there are conflicting data regarding susceptibility to herbivory. While some studies have documented that Ulva spp. were favored by a diversity of marine herbivores, other work has revealed herbivore deterrence. We investigated grazing and growth rates of the littorinid species, Littorina littorea and L. obtusata, when offered Fucus vesiculosus, Ascophyllum nodosum, Ulva lactuca, and Chondrus crispus, highlighting distinctive vulnerabilities to toxic effects of U. lactuca. Ulva lactuca was the preferred food of L. littorea, while L. obtusata showed no grazing on this ephemeral algal …

Gper/Gpr30, A Membrane Estrogen Receptor, Is Expressed In The Brain And Retina Of A Social Fish (Carassius Auratus) And Colocalizes With Isotocin, Lisa A. Mangiamele, Julia R. Gomez, Nancy J. Curtis, Richmond R. Thompson

Biological Sciences: Faculty Publications

Estradiol rapidly (within 30 minutes) influences a variety of sociosexual behaviors in both mammalian and nonmammalian vertebrates, including goldfish, in which it rapidly stimulates approach responses to the visual cues of females. Such rapid neuromodulatory effects are likely mediated via membrane-associated estrogen receptors; however, the localization and distribution of such receptors within the nervous system is not well described. To begin to address this gap, we identified GPER/GPR30, a G-protein-coupled estrogen receptor, in goldfish (Carassius auratus) neural tissue and used reverse-transcription polymerase chain reaction (RT-PCR) and in situ hybridization to test if GPR30 is expressed in the brain regions that …

Amoebozoans Are Secretly But Ancestrally Sexual: Evidence For Sex Genes And Potential Novel Crossover Pathways In Diverse Groups Of Amoebae, Yonas I. Tekle, Fiona C. Wood, Laura A. Katz, Mario A. Cero ́ N-Romero, Lydia A. Gorfu

Biological Sciences: Faculty Publications

Sex is beneficial in eukaryotes as it can increase genetic diversity, reshuffle their genomes, and purge deleterious mutations. Yet, its evolution remains a mystery. The eukaryotic clade supergroup Amoebozoa encompasses diverse lineages of polymorphic amoeboid forms, including both free-living and parasitic lineages. The group is generally believed to be asexual, though recent studies show that some of its members are implicated in cryptic forms of sexual cycles. In this study, we conduct a comprehensive inventory and analysis of genes involved in meiosis and related processes, in order to investigate the evolutionary history of sex in the clade. We analyzed genomic …

Rapid Turnover Of Ciliate Community Members In New England Tide Pools, Mary Badger, Sarah J. Tucker, Jean-David Grattepanche, Laura A. Katz

Biological Sciences: Faculty Publications

The rocky intertidal zone represents a dynamic habitat marked by considerable species richness, which has been well-documented for invertebrates and macroalgae. This high biodiversity exists in the context of extreme fluctuations in abiotic factors such as temperature, salinity and pH that occur during each tidal cycle. Despite these attributes, few studies have focused on microbial diversity in tide pools, including analyses of the ciliate communities that are the focus of this study. We investigated the spatial and temporal distributions of ciliate species across the intertidal environment at sites in Maine and Connecticut, USA. Our study used a DNA fingerprinting technique, …

Patchiness Of Ciliate Communities Sampled At Varying Spatial Scales Along The New England Shelf, Jean-David Grattepanche, George B. Mcmanus, Laura A. Katz

Biological Sciences: Faculty Publications

Although protists (microbial eukaryotes) provide an important link between bacteria and Metazoa in food webs, we do not yet have a clear understanding of the spatial scales on which protist diversity varies. Here, we use a combination of DNA fingerprinting (denaturant gradient gel electrophoresis or DGGE) and high-throughput sequencing (HTS) to assess the ciliate community in the class Spirotrichea at varying scales of 1–3 km sampled in three locations separated by at least 25 km—offshore, midshelf and inshore—along the New England shelf. Analyses of both abundant community (DGGE) and the total community (HTS) members reveal that: 1) ciliate communities are …

The Biodiversity Of Gastrointestinal Nematodes In South African Wildlife, Chalis J. Bird

Theses, Dissertations, and Projects

In this study, I investigated the diversity of parasites found in cheetah and wild ungulates in South Africa in collaboration with the Samara Private Game Reserve in Graaff Reinet, South Africa. Scat samples were collected over a period of two months, from September November, 2014, and DNA was extracted on the preserve for gastrointestinal nematode analysis. Wildlife was tracked using radio telemetry, tracks, and sign, while habitat and host distribution were documented. The aim was to determine the community composition of gastrointestinal nematodes in the wildlife hosts through molecular identification and to examine the role of host habitat preference, geographical …

Profiling The Macrofilaricidal Effects Of Flubendazole On Adult Female Brugia Malayi Using Rnaseq, Maeghan O'Neill, Cristina Ballesteros, Lucienne Tritten, Erica Burkman, Weam I. Zaky, Jianguo Xia, Andrew Moorhead, Steven A. Williams, Timothy G. Geary

Biological Sciences: Faculty Publications

The use of microfilaricidal drugs for the control of onchocerciasis and lymphatic filariasis (LF) necessitates prolonged yearly dosing. Prospects for elimination or eradication of these diseases would be enhanced by the availability of a macrofilaricidal drug. Flubendazole (FLBZ), a benzimidazole anthel- mintic, is an appealing candidate. FLBZ has demonstrated potent macrofilaricidal effects in a number of experimental rodent models and in one human trial. Unfortunately, FLBZ was deemed unsatisfactory for use in mass drug administration campaigns due to its limited oral bioavailability. A new formulation that enables sufficient bioavailability following oral administration could render FLBZ an effective treatment for onchocerciasis …

The Effects Of Ivermectin On Brugia Malayi Females In Vitro: A Transcriptomic Approach, Cristina Ballesteros, Lucienne Tritten, Maeghan O'Neill, Erica Burkman, Weam I. Zaky, Jianguo Xia, Andrew Moorhead, Steven A. Williams, Timothy G. Geary

Biological Sciences: Faculty Publications

Lymphatic filariasis and onchocerciasis are tropical diseases caused by infections with parasitic nematodes. Resulting chronic diseases can be strongly blinding and disfiguring, and contribute to an entrenched cycle of poverty in affected populations. Ivermectin is one of the pivotal drugs used to control these infections. The mechanism of antifilarial action of the drug is incompletely resolved. It kills circulating larval stages (microfilariae), but only reversibly sterilizes adult worms without killing them. Our limited understanding of the involved mechanisms hampers treatment optimization and sustainability of the efficacy of the drug, and investigations into its pharmacology are of paramount importance. Working with …

Radial Glia Inhibit Peripheral Glial Infiltration Into The Spinal Cord At Motor Exit Point Transition Zones, Cody J. Smith, Kimberly Johnson, Taylor G. Welsh, Michael J.F. Barresi, Sarah Kucenas

Biological Sciences: Faculty Publications

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 …

Gfap-Positive Radial Glial Cells Are An Essential Progenitor Population For Later-Born Neurons And Glia In The Zebrafish Spinal Cord, Kimberly Johnson, Jessica Barragan, Sarah Bashiruddin, Cody J. Smith, Chelsea Tyrrell, Michael J. Parsons, Rosemarie Doris, Sarah Kucenas, Gerald B. Downes, Carla M. Velez, Caitlin Schneider, Catalina Sakai, Narendra Pathak, Katrina Anderson, Rachael Stein, Stephen H. Devoto, Jeff S. Mumm, Michael J.F. Barresi

Biological Sciences: Faculty Publications

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+ …

Absence Of The Filarial Endosymbiont Wolbachia In Seal Heartworm (Acanthocheilonema Spirocauda) But Evidence Of Ancient Lateral Gene Transfer, Caroline D. Keroack, Jenna Irene Wurster, Caroline G. Decker, Kalini M. Williams, Barton E. Slatko, Jeremy M. Forster, Steven A. Williams

Biological Sciences: Faculty Publications

The symbiotic relationship of Wolbachia spp. was first observed in insects and subsequently in many parasitic filarial nematodes. This bacterium is believed to provide metabolic and developmental assistance to filarial parasitic nematodes, although the exact nature of this relationship remains to be fully elucidated. While Wolbachia is present in most filarial nematodes in the familyOnchocercidae, it is absent in several disparate species such as the human parasite Loa loa. All tested members of the genusAcanthocheilonema, such as Acanthocheilonema viteae, have been shown to lack Wolbachia. Consistent with this, we show thatWolbachia is absent from the seal heartworm (Acanthocheilonema spirocauda), but …

Increased Androgenic Sensitivity In The Hind Limb Muscular System Marks The Evolution Of A Derived Gestural Display, Lisa A. Mangiamele, Matthew J. Fuxjager, Eric R. Schuppe, Rebecca S. Taylor, Walter Hödl, Doris Preininger

Biological Sciences: Faculty Publications

Physical gestures are prominent features of many species’ multi- modal displays, yet how evolution incorporates body and leg movements into animal signaling repertoires is unclear. Andro- genic hormones modulate the production of reproductive signals and sexual motor skills in many vertebrates; therefore, one possi- bility is that selection for physical signals drives the evolution of androgenic sensitivity in select neuromotor pathways. We exam- ined this issue in the Bornean rock frog (Staurois parvus, family: Ranidae). Males court females and compete with rivals by per- forming both vocalizations and hind limb gestural signals, called “foot flags.” Foot flagging is a derived …

Phenotypic And Molecular Analysis Of The Effect Of 20-Hydroxyecdysone On The Human Filarial Parasite Brugia Malayi, Amruta S. Mhashilkar, Swamy R. Adapa, Rays H.Y. Jiang, Steven A. Williams, Weam I. Zaky, Barton E. Slatko, Ashley N. Luck, Andrew Moorhead, Thomas R. Unnasch

Biological Sciences: Faculty Publications

A homologue of the ecdysone receptor has been identified and shown to be responsive to 20- hydroxyecdysone in Brugia malayi. However, the role of this master regulator of insect development has not been delineated in filarial nematodes. Gravid adult female B. malayi cultured in the presence of 20-hydroxyecdysone produced significantly more microfilariae and abortive immature progeny than control worms, implicating the ecdysone receptor in regulation of embryogenesis and microfilarial development. Transcriptome analyses identified 30 genes whose expression was significantly up-regulated in 20-hydroxyecdysone-treated parasites compared with untreated controls. Of these, 18% were identified to be regulating transcription. A comparative proteomic analysis …

Nuclear Architecture And Patterns Of Molecular Evolution Are Correlated In The Ciliate Chilodonella Uncinata, Xyrus X. Maurer-Alcalá, Laura A. Katz

Biological Sciences: Faculty Publications

The relationship between nuclear architecture and patterns of molecular evolution in lineages across the eukaryotic tree of life is not well understood, partly because molecular evolution is traditionally explored as changes in base pairs along a linear sequence without considering the context of nuclear position of chromosomes. The ciliate Chilodonella uncinata is an ideal system to address the relationship between nuclear architecture and patterns of molecular evolution as the somatic macronucleus of this ciliate is composed of a peripheral DNA-rich area (orthomere) and a DNA-poor central region (paramere) to form a “heteromeric” macronucleus. Moreover, because the somatic chromosomes of C. …

A Novel Xenomonitoring Technique Using Mosquito Excreta/Feces For The Detection Of Filarial Parasites And Malaria, Nils Pilotte, Weam I. Zaky, Brian P. Abrams, Dave D. Chadee, Steven A. Williams

Biological Sciences: Faculty Publications

Given the continued successes of the world’s lymphatic filariasis (LF) elimination programs and the growing successes of many malaria elimination efforts, the necessity of low cost tools and methodologies applicable to long-term disease surveillance is greater than ever before. As many countries reach the end of their LF mass drug administration programs and a growing number of countries realize unprecedented successes in their malaria interven- tion efforts, the need for practical molecular xenomonitoring (MX), capable of providing surveillance for disease recrudescence in settings of decreased parasite prevalence is increasingly clear. Current protocols, however, require testing of mosquitoes in pools of …

Improved Pcr-Based Detection Of Soil Transmitted Helminth Infections Using A Next-Generation Sequencing Approach To Assay Design, Nils Pilotte, Marina Papaiakovou, Jessica R. Grant, Lou Ann Bierwert, Stacey Llewllyn, James S. Mccarthy, Steven A. Williams

Biological Sciences: Faculty Publications

The soil transmitted helminths are a group of parasitic worms responsible for extensive mor- bidity in many of the world’s most economically depressed locations. With growing empha- sis on disease mapping and eradication, the availability of accurate and cost-effective diagnostic measures is of paramount importance to global control and elimination efforts. While real-time PCR-based molecular detection assays have shown great promise, to date, these assays have utilized sub-optimal targets. By performing next-generation sequencing- based repeat analyses, we have identified high copy-number, non-coding DNA sequences from a series of soil transmitted pathogens. We have used these repetitive DNA elements as targets …

Human Xq28 Inversion Polymorphism: From Sex Linkage To Genomics - A Genetic Mother Lode, Cait S. Kirby, Natalie Kolber, Asmaa M. Salih Almohaidi, Lou Ann Bierwert, Lori Saunders, Steven Williams, Robert Merritt

Biological Sciences: Faculty Publications

An inversion polymorphism of the filamin and emerin genes at the tip of the long arm of the human X-chromosome serves as the basis of an investigative laboratory in which students learn something new about their own genomes. Long, nearly identical inverted repeats flanking the filamin and emerin genes illustrate how repetitive elements can lead to alterations in genome structure (inversions) through nonallelic homologous recombination. The near identity of the inverted repeats is an example of concerted evolution through gene conversion. While the laboratory in its entirety is designed for college level genetics courses, portions of the laboratory are appropriate …

Estrogens Suppress A Behavioral Phenotype In Zebrafish Mutants Of The Autism Risk Gene, Cntnap2, Ellen J. Hoffman, Katherine J. Turner, Joseph M. Fernandez, Daniel Cifuentes, Marcus Ghosh, Sundas Ijaz, Roshan A. Jain, Fumi Kubo, Brent R. Bill, Herwig Baier, Michael Granato, Michael J.F. Barresi, Stephen W. Wilson, Jason Rihel, Matthew W. State, Antonio J. Giraldez

Biological Sciences: Faculty Publications

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. …