Life Sciences Commons^™

Morphogenetic Defects Underlie Superior Coloboma, A Newly Identified Closure Disorder Of The Dorsal Eye, Jennifer C. Hocking, Jakub K. Famulski, Kevin H. Yoon, Sonya A. Widen, Cassidy S. Bernstein, Sophie Koch, Omri Weiss, Forge Canada Consortium, Canada, Seema Agarwala, Adi Inbal, Ordan J. Lehmann, Andrew J. Waskiewicz

Biology Faculty Publications

The eye primordium arises as a lateral outgrowth of the forebrain, with a transient fissure on the inferior side of the optic cup providing an entry point for developing blood vessels. Incomplete closure of the inferior ocular fissure results in coloboma, a disease characterized by gaps in the inferior eye and recognized as a significant cause of pediatric blindness. Here, we identify eight patients with defects in tissues of the superior eye, a congenital disorder that we term superior coloboma. The embryonic origin of superior coloboma could not be explained by conventional models of eye development, leading us to …

Highly Conserved Molecular Pathways, Including Wnt Signaling, Promote Functional Recovery From Spinal Cord Injury In Lampreys, Paige E. Herman, Angelos Papatheodorou, Stephanie A. Bryant, Courtney K. M. Waterbury, Joseph R. Herdy, Anthony A. Arcese, Joseph D. Buxbaum, Jeramiah J. Smith, Jennifer R. Morgan, Ona Bloom

Biology Faculty Publications

In mammals, spinal cord injury (SCI) leads to dramatic losses in neurons and synaptic connections, and consequently function. Unlike mammals, lampreys are vertebrates that undergo spontaneous regeneration and achieve functional recovery after SCI. Therefore our goal was to determine the complete transcriptional responses that occur after SCI in lampreys and to identify deeply conserved pathways that promote regeneration. We performed RNA-Seq on lamprey spinal cord and brain throughout the course of functional recovery. We describe complex transcriptional responses in the injured spinal cord, and somewhat surprisingly, also in the brain. Transcriptional responses to SCI in lampreys included transcription factor networks …

Ion Channel Signaling Influences Cellular Proliferation And Phagocyte Activity During Axolotl Tail Regeneration, Brandon M. Franklin, S. Randal Voss, Jeffrey L. Osborn

Biology Faculty Publications

Little is known about the potential for ion channels to regulate cellular behaviors during tissue regeneration. Here, we utilized an amphibian tail regeneration assay coupled with a chemical genetic screen to identify ion channel antagonists that altered critical cellular processes during regeneration. Inhibition of multiple ion channels either partially (anoctamin1/Tmem16a, anoctamin2/Tmem16b, K_V2.1, K_V2.2, L-type CaV channels and H/K ATPases) or completely (GlyR, GABA_AR, K_V1.5 and SERCA pumps) inhibited tail regeneration. Partial inhibition of tail regeneration by blocking the calcium activated chloride channels, anoctamin1&2, was associated with a reduction of cellular proliferation in …

A Linkage Map For The Newt Notophthalmus Viridescens: Insights In Vertebrate Genome And Chromosome Evolution, Melissa C. Keinath, S. Randal Voss, Panagiotis A. Tsonis, Jeramiah J. Smith

Biology Faculty Publications

Genetic linkage maps are fundamental resources that enable diverse genetic and genomic approaches, including quantitative trait locus (QTL) analyses and comparative studies of genome evolution. It is straightforward to build linkage maps for species that are amenable to laboratory culture and genetic crossing designs, and that have relatively small genomes and few chromosomes. It is more difficult to generate linkage maps for species that do not meet these criteria. Here, we introduce a method to rapidly build linkage maps for salamanders, which are known for their enormous genome sizes. As proof of principle, we developed a linkage map with thousands …

Variation In Dna Methylation Is Not Consistently Reflected By Sociality In Hymenoptera, Karl M. Glastad, Samuel V. Arsenault, Kim L. Vertacnik, Scott M. Geib, Sasha Kay, Bryan N. Danforth, Sandra M. Rehan, Catherine R. Linnen, Sarah D. Kocher, Brendan G. Hunt

Biology Faculty Publications

Changes in gene regulation that underlie phenotypic evolution can be encoded directly in the DNA sequence or mediated by chromatin modifications such as DNA methylation. It has been hypothesized that the evolution of eusocial division of labor is associated with enhanced gene regulatory potential, which may include expansions in DNA methylation in the genomes of Hymenoptera (bees, ants, wasps, and sawflies). Recently, this hypothesis garnered support from analyses of a commonly used metric to estimate DNA methylation in silico, CpG content. Here, we test this hypothesis using direct, nucleotide-level measures of DNA methylation across nine species of Hymenoptera. In doing …

Cellular And Molecular Features Of Developmentally Programmed Genome Rearrangement In A Vertebrate (Sea Lamprey: Petromyzon Marinus), Vladimir A. Timoshevskiy, Joseph R. Herdy, Melissa C. Keinath, Jeramiah J. Smith

Biology Faculty Publications

The sea lamprey (Petromyzon marinus) represents one of the few vertebrate species known to undergo large-scale programmatic elimination of genomic DNA over the course of its normal development. Programmed genome rearrangements (PGRs) result in the reproducible loss of ~20% of the genome from somatic cell lineages during early embryogenesis. Studies of PGR hold the potential to provide novel insights related to the maintenance of genome stability during the cell cycle and coordination between mechanisms responsible for the accurate distribution of chromosomes into daughter cells, yet little is known regarding the mechanistic basis or cellular context of PGR in …

Origin Of Amphibian And Avian Chromosomes By Fission, Fusion, And Retention Of Ancestral Chromosomes, Stephen R. Voss, D. Kevin Kump, Srikrishna Putta, Nathan Pauly, Anna Reynolds, Rema J. Henry, Saritha Basa, John A. Walker, Jeramiah J. Smith

Biology Faculty Publications

Amphibian genomes differ greatly in DNA content and chromosome size, morphology, and number. Investigations of this diversity are needed to identify mechanisms that have shaped the evolution of vertebrate genomes. We used comparative mapping to investigate the organization of genes in the Mexican axolotl (Ambystoma mexicanum), a species that presents relatively few chromosomes (n = 14) and a gigantic genome (>20 pg/N). We show extensive conservation of synteny between Ambystoma, chicken, and human, and a positive correlation between the length of conserved segments and genome size. Ambystoma segments are estimated to be four to 51 times longer than homologous …

Genic Regions Of A Large Salamander Genome Contain Long Introns And Novel Genes, Jeramiah J. Smith, Srikrishna Putta, Wei Zhu, Gerald M. Pao, Inder M. Verma, Tony Hunter, Susan V. Bryant, David M. Gardiner, Timothy T. Harkins, S. Randal Voss

Biology Faculty Publications

BACKGROUND: The basis of genome size variation remains an outstanding question because DNA sequence data are lacking for organisms with large genomes. Sixteen BAC clones from the Mexican axolotl (Ambystoma mexicanum: c-value = 32 x 10(9) bp) were isolated and sequenced to characterize the structure of genic regions.

RESULTS: Annotation of genes within BACs showed that axolotl introns are on average 10x longer than orthologous vertebrate introns and they are predicted to contain more functional elements, including miRNAs and snoRNAs. Loci were discovered within BACs for two novel EST transcripts that are differentially expressed during spinal cord regeneration and skin …

Effect Of Thyroid Hormone Concentration On The Transcriptional Response Underlying Induced Metamorphosis In The Mexican Axolotl (Ambystoma), Robert B. Page, Stephen R. Voss, Amy K. Samuels, Jeramiah J. Smith, Srikrishna Putta, Christopher K. Beachy

Biology Faculty Publications

BACKGROUND: Thyroid hormones (TH) induce gene expression programs that orchestrate amphibian metamorphosis. In contrast to anurans, many salamanders do not undergo metamorphosis in nature. However, they can be induced to undergo metamorphosis via exposure to thyroxine (T4). We induced metamorphosis in juvenile Mexican axolotls (Ambystoma mexicanum) using 5 and 50 nM T4, collected epidermal tissue from the head at four time points (Days 0, 2, 12, 28), and used microarray analysis to quantify mRNA abundances.

RESULTS: Individuals reared in the higher T4 concentration initiated morphological and transcriptional changes earlier and completed metamorphosis by Day 28. In contrast, initiation of metamorphosis …

Gene Order Data From A Model Amphibian (Ambystoma): New Perspectives On Vertebrate Genome Structure And Evolution, Jeramiah J. Smith, S. Randal Voss

Biology Faculty Publications

BACKGROUND: Because amphibians arise from a branch of the vertebrate evolutionary tree that is juxtaposed between fishes and amniotes, they provide important comparative perspective for reconstructing character changes that have occurred during vertebrate evolution. Here, we report the first comparative study of vertebrate genome structure that includes a representative amphibian. We used 491 transcribed sequences from a salamander (Ambystoma) genetic map and whole genome assemblies for human, mouse, rat, dog, chicken, zebrafish, and the freshwater pufferfish Tetraodon nigroviridis to compare gene orders and rearrangement rates.

RESULTS: Ambystoma has experienced a rate of genome rearrangement that is substantially lower than mammalian …

Drosophila Unpaired Encodes A Secreted Protein That Activates The Jak Signaling Pathway, Douglas A. Harrison, Patricia E. Mccoon, Richard Binari, Michael Gilman, Norbert Perrimon

Biology Faculty Publications

In vertebrates, many cytokines and growth factors have been identified as activators of the JAK/STAT signaling pathway. In Drosophila, JAK and STAT molecules have been isolated, but no ligands or receptors capable of activating the pathway have been described. We have characterized the unpaired (upd) gene, which displays the same distinctive embryonic mutant defects as mutations in the Drosophila JAK (hopscotch) and STAT (stat92E) genes. Upd is a secreted protein, associated with the extracellular matrix, that activates the JAK pathway. We propose that Upd is a ligand that relies on JAK signaling to stimulate transcription of pair-rule genes in a …