Danielle Herrig and Autumn Marsden will Present their Research Thursday, 7/10/14

Danielle’s Abstract

SPECIATION GENETICS IN DROSPHILA: INSIGHTS FROM GENES, GENOMES, AND TRANSCRIPTOMES (YEAR 3)

Speciation typically occurs when a single species splits into two populations in which gene flow is severely reduced. Over time, the two populations accumulate genetic differences that eventually produce two independent species. While hybridization between two species, and thus the potential for gene exchange, has traditionally been viewed as a reproductive mistake, recent studies suggest that it is not as rare as once believed. Previous studies suggest that although regions of the mitochondrial and nuclear genomes can be exchanged independently or together, the X chromosome often plays a large role in speciation and gene exchange is typically barred on the X. One way in which the X chromosome may play a large role in speciation is though X-linked trans-regulatory elements (TREs) effecting the expression of autosomal genes through interactions with autosomal cis-regulatory elements (CREs). Indeed, whole-genome analyses of gene expression in our lab indicate that X-linked genes are more differentially expressed between species while autosomal genes are preferentially misexpressed in hybrid males. Because there is only one copy of the X chromosome producing X-linked TREs in hybrid males, we hypothesize that the hemizygosity of the X chromosome leads to greater levels of autosomal misexpression in the heterogametic sex. To investigate the effects of the uni-parental origin of the X chromosome on autosomal misexpression, we will analyze whole-genome expression in attached-X stocks of Drosophila yakuba, D. santomea, and their hybrids wherein the X chromosomes are inherited in a uni-parental manner in females. It is my expectation that if the hemizygosity of the X chromosome contributes to autosomal misexpression in males, attached-X F1 hybrid females will mimic results from F1 hybrid males.

Autumn’s Abstract

Calcium-dependent Naked-Dishevelled Interaction Modulates Wnt Signalling Outputs

AN Marsden1,2, SW Derry1, TA Westfall1, DC Slusarski1

1Department of Biology, University of Iowa, Iowa City, IA 52242, 2Interdisciplinary Graduate Program in Genetics

The Wnt signaling network plays critical roles in development and is implicated in human disease. Wnts comprise a complex signaling network that, upon ligand binding, activates the phosphoprotein Dishevelled (Dvl), leading to distinct outputs including polarized cell movement (known as planar cell polarity, Wnt/PCP) and stabilization of the transcription factor β-catenin (Wnt/β-catenin). The mechanisms that determine a specific output is not completely understood, especially since they share receptors and cellular effectors. My project focuses on two such shared components that also bind each other, Dvl and Naked (Nkd). Previously we demonstrated that Nkd is required for zebrafish dorsal forerunner cell (DFC) migration, Kupffer’s vesicle formation and proper organ laterality. Moreover, we identified calcium fluxes in the DFCs and determined that the EF-hand motif in Nkd weakly binds calcium. Using a combination of biochemical and functional assays, we show calcium-induced conformational changes in the Nkd-Dvl complex and identify a requirement for the Nkd EF-hand in cell polarity but not in β-catenin transcriptional outputs. We predict that Nkd and Dvl form a cooperative calcium binding pocket, which allows for conformational changes or subcellular localization to direct Wnt/PCP output. We identified a region in Dvl that may coordinate ion binding. We have mutated this novel Dvl calcium binding site, and performed biochemical, genetic, and functional studies. To determine the impact upon Wnt signaling output, I utilize gene knockdown and rescue in the zebrafish DFCs, in a tissue that hosts converging Wnt signals. I also determined the subcellular localization of Nkd and Dvl components within the cells known to have calcium fluxes and cells that are quiescent. Our data suggests that calcium-induced secondary structure changes in the Nkd-Dvl complex serve to interpret the physiology of a cell receiving multiple cues and provides mechanistic insight into Wnt signal integration in vivo.

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Posted on July 7, 2014, in Student Seminar. Bookmark the permalink. Leave a comment.

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