Researcher:
Dunn, Gülayşe İnce

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Gülayşe İnce

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Dunn

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Dunn, Gülayşe İnce

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2014 - 201952020 - 20211

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    NEUROD2 transcription factor regulates expression of Id2 gene during neuronal differentiation
    (Wiley-Blackwell, 2014) N/A; N/A; N/A; Department of Molecular Biology and Genetics; Güzelsoy, Gizem; Bayam, Efil; Dunn, Gülayşe İnce; Master Student; Researcher; Other; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; N/A
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    Roles of nelavl in Kif2a pre-mrna splicing and functional roles of KIF2A protein isoforms
    (Wiley-Blackwell, 2014) Bayam, Emrah; N/A; N/A; N/A; Department of Molecular Biology and Genetics; Akkaya, Cansu; Güner, Gökhan; Dunn, Gülayşe İnce; PhD Student; Master Student; Other; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; N/A
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    NEUROD2 regulates stim1 expression and store-operated calcium entry in cortical neurons
    (Soc Neuroscience, 2017) N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; Department of Physics; Department of Molecular Biology and Genetics; Güner, Gökhan; Güzelsoy, Gizem; İşleyen, Fatma Sadife; Şahin, Gülcan Semra; Akkaya, Cansu; Bayam, Efil; Kotan, Ilgın Eser; Kabakçıoğlu, Alkan; Dunn, Gülayşe İnce; Master Student; Master Student; Master Student; Master Student; PhD Student; Researcher; Master Student; Faculty Member; Other; Department of Physics; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Sciences; College of Sciences; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 49854; N/A
    Calcium signaling controls many key processes in neurons, including gene expression, axon guidance, and synaptic plasticity. In contrast to calcium influx through voltage- or neurotransmitter-gated channels, regulatory pathways that control store-operated calcium entry (SOCE) in neurons are poorly understood. Here, we report a transcriptional control of Stim1 (stromal interaction molecule 1) gene, which is a major sensor of endoplasmic reticulum (ER) calcium levels and a regulator of SOCE. By using a genome-wide chromatin immunoprecipitation and sequencing approach in mice, we find that NEUROD2, a neurogenic transcription factor, binds to an intronic element within the Stim1 gene. We show that NEUROD2 limits Stim1 expression in cortical neurons and consequently fine-tunes the SOCE response upon depletion of ER calcium. Our findings reveal a novel mechanism that regulates neuronal calcium homeostasis during cortical development.
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    Roles of developmentally regulated KIF2A alternative isoforms in cortical neuron migration and differentiation
    (The Company of Biologists, 2021) N/A; N/A; N/A; N/A; N/A; N/A; N/A; Department of Molecular Biology and Genetics; N/A; Akkaya, Cansu; Atak, Dila; Kamacıoğlu, Altuğ; Akarlar, Büşra; Güner, Gökhan; Bayam, Efil; Taşkın, Ali Cihan; Dunn, Gülayşe İnce; PhD Student; PhD Student; Master Student; Other; Master Student; Researcher; Other; Faculty Member; Other; Department of Molecular Biology and Genetics; N/A; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; N/A; Graduate School of Sciences and Engineering; N/A; N/A; College of Sciences; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 291296; 105301; N/A
    KIF2A is a kinesin motor protein with essential roles in neural progenitor division and axonal pruning during brain development. However, how different KIF2A alternative isoforms function during development of the cerebral cortex is not known. Here, we focus on three Kif2a isoforms expressed in the developing cortex. We show that Kif2a is essential for dendritic arborization in mice and that the functions of all three isoforms are sufficient for this process. Interestingly, only two of the isoforms can sustain radial migration of cortical neurons; a third isoform, lacking a key N-terminal region, is ineffective. By proximity-based interactome mapping for individual isoforms, we identify previously known KIF2A interactors, proteins localized to the mitotic spindle poles and, unexpectedly, also translation factors, ribonucleoproteins and proteins that are targeted to organelles, prominently to the mitochondria. In addition, we show that a KIF2A mutation, which causes brain malformations in humans, has extensive changes to its proximity-based interactome, with depletion of mitochondrial proteins identified in the wild-type KIF2A interactome. Our data raises new insights about the importance of alternative splice variants during brain development.
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    PublicationOpen Access
    Terminal neuron localization to the upper cortical plate is controlled by the transcription factor NEUROD2
    (Nature Publishing Group (NPG), 2019) Department of Molecular Biology and Genetics; Department of Physics; Akkaya, Cansu; Atak, Dila; Güzelsoy, Gizem; Dunn, Cory David; Dunn, Gülayşe İnce; Kabakçıoğlu, Alkan; Master Student; Faculty Member; Faculty Member; Faculty Member; Department of Molecular Biology and Genetics; Department of Physics; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; N/A; N/A; 105301; N/A; 49854
    Excitatory neurons of the mammalian cerebral cortex are organized into six functional layers characterized by unique patterns of connectivity, as well as distinctive physiological and morphological properties. Cortical layers appear after a highly regulated migration process in which cells move from the deeper, proliferative zone toward the superficial layers. Importantly, defects in this radial migration process have been implicated in neurodevelopmental and psychiatric diseases. Here we report that during the final stages of migration, transcription factor Neurogenic Differentiation 2 (Neurod2) contributes to terminal cellular localization within the cortical plate. In mice, in utero knockdown of Neurod2 resulted in reduced numbers of neurons localized to the uppermost region of the developing cortex, also termed the primitive cortical zone. Our ChIP-Seq and RNA-Seq analyses of genes regulated by NEUROD2 in the developing cortex identified a number of key target genes with known roles in Reelin signaling, a critical regulator of neuronal migration. Our focused analysis of regulation of the Reln gene, encoding the extracellular ligand REELIN, uncovered NEUROD2 binding to conserved E-box elements in multiple introns. Furthermore, we demonstrate that knockdown of NEUROD2 in primary cortical neurons resulted in a strong increase in Reln gene expression at the mRNA level, as well as a slight upregulation at the protein level. These data reveal a new role for NEUROD2 during the late stages of neuronal migration, and our analysis of its genomic targets offers new genes with potential roles in cortical lamination.
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    PublicationOpen Access
    Genome-wide target analysis of NEUROD2 provides new insights into regulation of cortical projection neuron migration and differentiation
    (BioMed Central, 2015) Department of Molecular Biology and Genetics; Department of Physics; Bayam, Efil; Şahin, Gülcan Semra; Güzelsoy, Gizem; Güner, Pınar Tatar; Kabakçıoğlu, Alkan; Dunn, Gülayşe İnce; Teaching Faculty; Faculty Member; Department of Molecular Biology and Genetics; Department of Physics; College of Sciences; N/A; N/A; N/A; 188227; 49854; N/A
    Background: Cellular differentiation programs are controlled, to a large extent, by the combinatorial functioning of specific transcription factors. Corticalprojection neurons constitute the major excitatory neuron population within the cortex and mediate long distance communication between the cortex and other brain regions. Our understanding of effector transcription factors and their downstream transcriptional programs that direct the differentiation process ofcortical projection neurons is far from complete. Results: In this study, we carried out a ChIP-Seq (chromatin-immunoprecipitation and sequencing) analysis of NEUROD2, an effector transcription factor expressed in lineages of cortical projection neurons during the peak of cortical excitatory neurogenesis. Our results suggest that during cortical developmentNEUROD2 targets key genes that are required for Reelin signaling, a major pathway that regulates the migration of neurons from germinal zones to their final layers of residence within the cortex. We also find that NEUROD2 binds to a large set of genes with functions in layer-specific differentiation and in axonal pathfinding of cortical projection neurons. Conclusions: Our analysis of in vivo NEUROD2 target genes offers mechanistic insight into signaling pathways that regulate neuronal migration and axon guidance and identifies genes that are likely to be required for proper cortical development.