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Developmental Biology

2013

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Articles 1 - 14 of 14

Full-Text Articles in Molecular Biology

Hdac6 Regulates Tip60-P400 Function In Stem Cells, Poshen B. Chen, Jui-Hung Hung, Taylor L. Hickman, Andrew H. Coles, James F. Carey, Zhiping Weng, Feixia Chu, Thomas G. Fazzio Dec 2013

Hdac6 Regulates Tip60-P400 Function In Stem Cells, Poshen B. Chen, Jui-Hung Hung, Taylor L. Hickman, Andrew H. Coles, James F. Carey, Zhiping Weng, Feixia Chu, Thomas G. Fazzio

Program in Molecular Medicine Publications and Presentations

In embryonic stem cells (ESCs), the Tip60 histone acetyltransferase activates genes required for proliferation and silences genes that promote differentiation. Here we show that the class II histone deacetylase Hdac6 co-purifies with Tip60-p400 complex from ESCs. Hdac6 is necessary for regulation of most Tip60-p400 target genes, particularly those repressed by the complex. Unlike differentiated cells, where Hdac6 is mainly cytoplasmic, Hdac6 is largely nuclear in ESCs, neural stem cells (NSCs), and some cancer cell lines, and interacts with Tip60-p400 in each. Hdac6 localizes to promoters bound by Tip60-p400 in ESCs, binding downstream of transcription start sites. Surprisingly, Hdac6 does not ...


The Development Of An In Vivo Microdialysis Collection Method Of Cytokines From Brain Tissue, Anthony W. Herbaugh Dec 2013

The Development Of An In Vivo Microdialysis Collection Method Of Cytokines From Brain Tissue, Anthony W. Herbaugh

Theses and Dissertations

In this thesis, different methods to improve the microdialysis collection procedure for cytokines from brain tissue are presented. The first method was based on stopped flow and results indicating that no significant difference in relative recovery between stopped flow and continuous flow are shown. The second method is an antibody bead-based enhancement method. With the antibody bead-based method, a 3.5 fold increase in the collected concentrations of Chemokine (C-C motif) Ligand 2 (CCL2) were observed. However, there was no significant increase in the in vivo collection efficiency of Interleukin-6 (IL-6) using the antibody enhancement. Finally the development of an ...


Id2 Complexes With The Snag Domain Of Snai1 Inhibiting Snai1-Mediated Repression Of Integrin Beta4, Cheng Chang, Xiaofang Yang, Bryan Pursell, Arthur M. Mercurio Oct 2013

Id2 Complexes With The Snag Domain Of Snai1 Inhibiting Snai1-Mediated Repression Of Integrin Beta4, Cheng Chang, Xiaofang Yang, Bryan Pursell, Arthur M. Mercurio

Cancer Biology Publications and Presentations

The epithelial-mesenchymal transition (EMT) is a fundamental process that underlies development and cancer. Although the EMT involves alterations in the expression of specific integrins that mediate stable adhesion to the basement membrane, such as alpha6beta4, the mechanisms involved are poorly understood. Here, we report that Snai1 inhibits beta4 transcription by increasing repressive histone modification (trimethylation of histone H3 at K27 [H3K27Me3]). Surprisingly, Snai1 is expressed and localized in the nucleus in epithelial cells, but it does not repress beta4. We resolved this paradox by discovering that Id2 complexes with the SNAG domain of Snai1 on the beta4 promoter and constrains ...


Characterization Of A Glycosyphosphatidylinositol Anchor Transamidase In Arabidopsis Thaliana And The Function Of Gpi Anchored Proteins In Stomatal Development, Mark Gerald Ronald Bundy Aug 2013

Characterization Of A Glycosyphosphatidylinositol Anchor Transamidase In Arabidopsis Thaliana And The Function Of Gpi Anchored Proteins In Stomatal Development, Mark Gerald Ronald Bundy

Masters Theses

In plants stomata play a vital role for survival by allowing the gas exchange of CO2 [carbon dioxide] and water vapor to occur. A stoma is a central pore flanked by two kidney shaped guard cells and in wild type there is at least one pavement cell between each stoma. The ERECTA (ER) gene family consisting of ER, ERL1, ERL2 is involved in regulation of stomata development, where a triple mutant of er erl1 erl2 displays an increased stomata index and clusters of stomata that disobey the one cell spacing rule. To better understand the pathway of stomata development ...


Molecular Mechanisms Underlying The Early Life Programming Of The Liver, Gurjeev Sohi Jul 2013

Molecular Mechanisms Underlying The Early Life Programming Of The Liver, Gurjeev Sohi

Electronic Thesis and Dissertation Repository

Clinical studies have demonstrated that intrauterine growth restriction (IUGR) offspring, faced with a nutritional mismatch postpartum, have an increased risk of developing the metabolic syndrome. The maternal protein restriction (MPR) rat model has been extensively studied to investigate the adverse effects of a nutritional mismatch in postnatal life of IUGR offspring. Previous studies have demonstrated that MPR leads to impaired function of the liver, an important metabolic organ. However the underlying mechanisms which predispose these offspring to the metabolic syndrome remain elusive. In the following studies, low protein diet during pregnancy and lactation led to IUGR offspring with decreased liver ...


The Scaffold Attachment Factor B1 (Safb1) Regulates Myogenic Differentiation By Facilitating The Transition Of Myogenic Gene Chromatin From A Repressed To An Activated State, J. Manuel Hernandez-Hernandez, Chandrashekara Mallappa, Brian T. Nasipak, Steffi Oesterreich, Anthony N. Imbalzano Jun 2013

The Scaffold Attachment Factor B1 (Safb1) Regulates Myogenic Differentiation By Facilitating The Transition Of Myogenic Gene Chromatin From A Repressed To An Activated State, J. Manuel Hernandez-Hernandez, Chandrashekara Mallappa, Brian T. Nasipak, Steffi Oesterreich, Anthony N. Imbalzano

University of Massachusetts Medical School Faculty Publications

The regulation of skeletal muscle gene expression during myogenesis is mediated by lineage-specific transcription factors in combination with numerous cofactors, many of which modify chromatin structure. However, the involvement of scaffolding proteins that organize chromatin and chromatin-associated regulatory proteins has not extensively been explored in myogenic differentiation. Here, we report that Scaffold attachment factor b1 (Safb1), primarily associated with transcriptional repression, functions as a positive regulator of myogenic differentiation. Knockdown of Safb1 inhibited skeletal muscle marker gene expression and differentiation in cultured C2C12 myoblasts. In contrast, over-expression resulted in the premature expression of critical muscle structural proteins and formation of ...


Victor Ambros: The Broad Scope Of Micrornas. Interview By Caitlin Sedwick, Victor R. Ambros May 2013

Victor Ambros: The Broad Scope Of Micrornas. Interview By Caitlin Sedwick, Victor R. Ambros

Program in Molecular Medicine Publications and Presentations

Interview with Victor Ambros, who studies how microRNAs impact development.


Role Of Map4k4 In Skeletal Muscle Differentiation: A Dissertation, Mengxi Wang May 2013

Role Of Map4k4 In Skeletal Muscle Differentiation: A Dissertation, Mengxi Wang

GSBS Dissertations and Theses

Skeletal muscle is a complicated and heterogeneous striated muscle tissue that serves critical mechanical and metabolic functions in the organism. The process of generating skeletal muscle, myogenesis, is elaborately coordinated by members of the protein kinase family, which transmit diverse signals initiated by extracellular stimuli to myogenic transcriptional hierarchy in muscle cells. Mitogen-activated protein kinases (MAPKs) including p38 MAPK, c-Jun N terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) are components of serine/threonine protein kinase cascades that play important roles in skeletal muscle differentiation. The exploration of MAPK upstream kinases identified mitogen activated protein kinase kinase kinase kinase ...


Stress Granules As Crucibles Of Als Pathogenesis, Yun R. Li, Oliver D. King, James Shorter, Aaron D. Gitler Apr 2013

Stress Granules As Crucibles Of Als Pathogenesis, Yun R. Li, Oliver D. King, James Shorter, Aaron D. Gitler

Wellstone Center for FSHD Publications

Amyotrophic lateral sclerosis (ALS) is a fatal human neurodegenerative disease affecting primarily motor neurons. Two RNA-binding proteins, TDP-43 and FUS, aggregate in the degenerating motor neurons of ALS patients, and mutations in the genes encoding these proteins cause some forms of ALS. TDP-43 and FUS and several related RNA-binding proteins harbor aggregation-promoting prion-like domains that allow them to rapidly self-associate. This property is critical for the formation and dynamics of cellular ribonucleoprotein granules, the crucibles of RNA metabolism and homeostasis. Recent work connecting TDP-43 and FUS to stress granules has suggested how this cellular pathway, which involves protein aggregation as ...


The Function Of Centralspindlin In Drosophila Development, Michael Craig Sfregola Jan 2013

The Function Of Centralspindlin In Drosophila Development, Michael Craig Sfregola

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Centralspindlin is an essential protein complex in all metazoans well-studied for its essential role in cytokinesis. Emerging evidence suggests centralspindlin has important interphase functions as well. Through its regulation of Rho family small GTPases at the plasma membrane, the centralspindlin complex is able to effect a number of cellular process including cell adhesion and cell migration. In this thesis I explored centralspindlin's function in development and tissue morphogenesis. In addition I investigated potential nuclear functions of the centralspindlin complex. To address these potential functions of centralspindlin I used the model organism Drosophila melanogaster.

I found centralspindlin is essential for ...


Regulation Of C. Elegans Developmental Timing By The Gata Transcription Factor Elt-1, Max Louis Cohen Jan 2013

Regulation Of C. Elegans Developmental Timing By The Gata Transcription Factor Elt-1, Max Louis Cohen

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The heterochronic gene network controls developmental timing in the nematode roundworm Caenorhabditis elegans. Bi-stable switch-like changes in gene expression occur during its development as stage-specific microRNAs are expressed and subsequently down-regulate other stage-specific factors, allowing for developmental progression. Key genes in this regulatory network are phylogenetically conserved and include the post-transcriptional microRNA repressor lin-28; the nuclear hormone receptor daf-12; and the microRNAs lin-4, mir-48, mir-84, mir-241, and let-7. daf-12 is the only factor currently known to regulate transcription of the Let-7 microRNA family, but its contribution is insufficient to account for all of the transcriptional regulation observed. In this work ...


Genomic Analysis Of Micrornas In Mouse Skin: Quantification, Biogenesis, Target Recognition And Regulatory Functions, Zhaojie Zhang Jan 2013

Genomic Analysis Of Micrornas In Mouse Skin: Quantification, Biogenesis, Target Recognition And Regulatory Functions, Zhaojie Zhang

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

MiRNAs are a class of small RNAs, approximately 20~22 nucleotides in length. These broadly conserved molecules represent a novel layer of gene regulation that fine-tunes the output of the transcriptome and contributes to the robustness of biological pathways. However, the quantitative picture of the miRNA pathway is unclear. Fundamental questions concerning the biogenesis pathway, target recognition and regulatory functions of individual miRNAs within mammalian tissues remain poorly understood. In this thesis, I employ mouse skin as a model system to examine the miRNA pathway with genomic approaches.

I profiled the expression of miRNAs in mouse skin with a small ...


Cellular Mechanisms Of Mammalian Liver Regeneration, Kilangsungla Yanger Jan 2013

Cellular Mechanisms Of Mammalian Liver Regeneration, Kilangsungla Yanger

Publicly Accessible Penn Dissertations

ABSTRACT

CELLULAR MECHANISMS OF MAMMALIAN LIVER REGENERATION

Kilangsungla Yanger

Ben Z. Stanger

The liver is an essential organ that aids in metabolic processes, protein synthesis and detoxification of harmful substances. As the centre for detoxification, the liver is able to compensate for this routine damage with its robust regenerative ability. All vertebrate livers, for example, can make up for tissue mass loss (via surgical excision of a portion of the liver) by replication of their differentiated cells within the remnant lobes. These differentiated cells include parenchymal cells such as the hepatocytes and biliary epithelial cells (BECs) and also non-parenchymal cells ...


Abnormal Smooth Muscle Contraction Alters Gut Motility And Propagates Epithelial Invasion In The Larval Zebrafish Intestine, Joshua Abrams Jan 2013

Abnormal Smooth Muscle Contraction Alters Gut Motility And Propagates Epithelial Invasion In The Larval Zebrafish Intestine, Joshua Abrams

Publicly Accessible Penn Dissertations

Coordinated smooth muscle contraction is critical for force production and proper functioning of numerous organ systems. Activation at the myosin motor domain via phosphorylated myosin light chain (phospho-MLC) remains the primary signal to initiate contraction, but it is now appreciated that there are additional force modulators also present in smooth muscle. One particularly well studied modulatory protein is Caldesmon (CaD), which has been implicated in controlling contractile force in vascular smooth muscle, however little is known of CaD's physiological role in vivo. Studies in vitro have shown that CaD inhibits actomyosin interactions and that this effect is reversed after ...