subject:(Cadherins Research)

1. Cooper, Sharon Rose. δ-Protocadherin Function: From Molecular Adhesion Properties to Brain Circuitry.

Degree: PhD, Molecular, Cellular and Developmental Biology, 2017, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1492457066344753

► Selective cell-to-cell adhesion is essential for normal development of the vertebrate brain, contributing to coordinated cell movements, regional partitioning and synapse formation. Members of the… (more)

▼ Selective cell-to-cell adhesion is essential for normal development of the vertebrate brain, contributing to coordinated cell movements, regional partitioning and synapse formation. Members of the cadherin superfamily mediate calcium-dependent cell adhesion, and selective adhesion by various family members is thought to contribute to the development of neural circuitry. Members of the δ-protocadherin subfamily of cadherins are differentially expressed in the vertebrate nervous system and have been implicated in a range of neurodevelopmental disorders: schizophrenia, mental retardation, and epilepsy. However, little is known about how the δ-protocadherins contribute to the development of the nervous system, nor how this development is disrupted in the disease state.Here I focus on one member of the δ-protocadherin family, protocadherin-19 (pcdh19), since it has the clearest link to a neurodevelopmental disease, being the second most clinically relevant gene in epilepsy. Using pcdh19 transgenic zebrafish, we observed columnar modules of pcdh19-expresing cells in the optic tectum. In the absence of Pcdh19, the columnar organization is disrupted and visually guided behaviors are impaired. Furthermore, similar columns were observed in pcdh1a transgenic zebrafish, located both in the tectum and in other brain regions. This suggests protocadherin defined columns may be a theme of neural development. Our X-ray crystal structure of Pcdh19 reveals the adhesion interface for Pcdh19 and infers the molecular consequences of epilepsy causing mutations. We found several epilepsy causing mutations were located at the interface and disrupted adhesion, which further validated the interface and revealed a possible biochemical cause of Pcdh19 dysfunction. Furthermore, sequence alignments of other δ-protocadherins with Pcdh19 suggest that this interface may be relevant to the entire δ-protocadherin subfamily.We used the information gained about Pcdh19 to design PCDH19-FE mutations in the genome of zebrafish for comparing the circuitry of embryos with wild-type pcdh19, non-adhesive pcdh19 or without pcdh19. The combination of in vitro adhesion studies and in vivo brain imaging analysis provides a more comprehensive understanding of protocadherin-19 function, and suggests a broader role for the δ-protocadherin family in differential adhesion during brain development. Advisors/Committee Members: Jontes, James (Advisor), Sotomayor, Marcos (Advisor).

Subjects/Keywords: Biochemistry; Biology; Biomedical Research; Developmental Biology; Molecular Biology; Neurosciences; Biophysics; Cellular Biology; epilepsy; EFMR; Pcdh19; protocadherins; cadherins; calcium binding; adhesion; neurons; neural circuitry; neural development; brain development; neuroscience; biophysics; structural biology; zebrafish; superior colliculus; optic tectum; TALEN

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APA (6^th Edition):

Cooper, S. R. (2017). δ-Protocadherin Function: From Molecular Adhesion Properties to Brain Circuitry. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1492457066344753

Chicago Manual of Style (16^th Edition):

Cooper, Sharon Rose. “δ-Protocadherin Function: From Molecular Adhesion Properties to Brain Circuitry.” 2017. Doctoral Dissertation, The Ohio State University. Accessed April 22, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1492457066344753.

MLA Handbook (7^th Edition):

Cooper, Sharon Rose. “δ-Protocadherin Function: From Molecular Adhesion Properties to Brain Circuitry.” 2017. Web. 22 Apr 2021.

Vancouver:

Cooper SR. δ-Protocadherin Function: From Molecular Adhesion Properties to Brain Circuitry. [Internet] [Doctoral dissertation]. The Ohio State University; 2017. [cited 2021 Apr 22]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1492457066344753.

Council of Science Editors:

Cooper SR. δ-Protocadherin Function: From Molecular Adhesion Properties to Brain Circuitry. [Doctoral Dissertation]. The Ohio State University; 2017. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1492457066344753

2. Lin, Yu-Hung. Probing cellular mechano-sensitivity using biomembrane-mimicking cell substrates of adjustable stiffness.

Degree: 2015, IUPUI

URL: http://hdl.handle.net/1805/9965

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Indiana University-Purdue University Indianapolis (IUPUI)

It is increasingly recognized that mechanical properties of substrates play a pivotal role in the regulation of cellular fate and… (more)

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Indiana University-Purdue University Indianapolis (IUPUI)

It is increasingly recognized that mechanical properties of substrates play a pivotal role in the regulation of cellular fate and function. However, the underlying mechanisms of cellular mechanosensing still remain a topic of open debate. Traditionally, advancements in this field have been made using polymeric substrates of adjustable stiffness with immobilized linkers. While such substrates are well suited to examine cell adhesion and migration in an extracellular matrix environment, they are limited in their ability to replicate the rich dynamics found at cell-cell interfaces. To address this challenge, we recently introduced a linker-functionalized polymer-tethered multi-bilayer stack, in which substrate stiffness can be altered by the degree of bilayer stacking, thus allowing the analysis of cellular mechanosensitivity. Here, we apply this novel biomembrane-mimicking cell substrate design to explore the mechanosensitivity of C2C12 myoblasts in the presence of cell-cell-mimicking N-cadherin linkers. Experiments are presented, which demonstrate a relationship between the degree of bilayer stacking and mechanoresponse of plated cells, such as morphology, cytoskeletal organization, cellular traction forces, and migration speed. Furthermore, we illustrate the dynamic assembly of bilayer-bound N-cadherin linkers underneath cellular adherens junctions. In addition, properties of individual and clustered N-cadherins are examined in the polymer-tethered bilayer system in the absence of plated cells. Alternatively, substrate stiffness can be adjusted by the concentration of lipopolymers in a single polymer-tethered lipid bilayer. On the basis of this alternative cell substrate concept, we also discuss recent results on a linker-functionalized single polymer-tethered bilayer substrate with a lateral gradient in lipopolymer concentration (substrate viscoelasticity). Specifically, we show that the lipopolymer gradient has a notable impact on spreading, cytoskeletal organization, and motility of 3T3 fibroblasts. Two cases are discussed: 1. polymer-tethered bilayers with a sharp boundary between low and high lipopolymer concentration regions and 2. polymer-tethered bilayers with a gradual gradient in lipopolymer concentration.

Advisors/Committee Members: Naumann, Christoph A., Das, Chittaranjan, Thompson, David, Long, Eric C..

Subjects/Keywords: Artificial Substrate; Cadherin; Polymer-tethered Bilayer; Biomembrane-mimicking; Lipid Bilayer; Cadherins – Research; Cell junctions – Research; Polymers – Surfaces; Bilayer lipid membranes – Research; Cell adhesion – Research – Analysis; Biological interfaces – Research – Analysis; Cellular control mechanisms – Research; Cells – Mechanical properties – Research; Polymers – Rheology; Artificial cells – Research

…clustered N-cadherins are examined in the polymer-tethered bilayer system in the absence of plated… …1 INTRODUCTION 1.1 Rationale and Objective For decades, most research related to the… …have a different mechanoresponse, and in turn different cytoskeleton organization. Research… …systems. The research described within this dissertation focuses on the development of…

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APA (6^th Edition):

Lin, Y. (2015). Probing cellular mechano-sensitivity using biomembrane-mimicking cell substrates of adjustable stiffness. (Thesis). IUPUI. Retrieved from http://hdl.handle.net/1805/9965

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lin, Yu-Hung. “Probing cellular mechano-sensitivity using biomembrane-mimicking cell substrates of adjustable stiffness.” 2015. Thesis, IUPUI. Accessed April 22, 2021. http://hdl.handle.net/1805/9965.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lin, Yu-Hung. “Probing cellular mechano-sensitivity using biomembrane-mimicking cell substrates of adjustable stiffness.” 2015. Web. 22 Apr 2021.

Vancouver:

Lin Y. Probing cellular mechano-sensitivity using biomembrane-mimicking cell substrates of adjustable stiffness. [Internet] [Thesis]. IUPUI; 2015. [cited 2021 Apr 22]. Available from: http://hdl.handle.net/1805/9965.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lin Y. Probing cellular mechano-sensitivity using biomembrane-mimicking cell substrates of adjustable stiffness. [Thesis]. IUPUI; 2015. Available from: http://hdl.handle.net/1805/9965

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Florida

3. McGarry, Michelle Ann, 1975-. Benzo(a)pyrene-mediated effects on cellular adhesion and signal transduction pathways in endometrial cancer.

Degree: 2001, University of Florida

URL: https://ufdc.ufl.edu/AA00022176

Subjects/Keywords: Actins; Cadherins; Cell adhesion; Cell cycle; Cell lines; Cell membranes; Cells; Genes; Oxidative stress; Xenobiotics; Benzo(a)pyrene – pharmacology ( mesh ); Cell Adhesion ( mesh ); Cell Cycle ( mesh ); Cytochrome P-450 CYP1A1 ( mesh ); Cytoskeleton ( mesh ); Department of Pharmacology and Therapeutics thesis Ph.D ( mesh ); Dioxins – pharmacology ( mesh ); Endometrial Neoplasms ( mesh ); Research ( mesh ); Signal Transduction ( mesh ); Tumor Cells, Cultured ( mesh )

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

McGarry, Michelle Ann, 1. (2001). Benzo(a)pyrene-mediated effects on cellular adhesion and signal transduction pathways in endometrial cancer. (Thesis). University of Florida. Retrieved from https://ufdc.ufl.edu/AA00022176

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

McGarry, Michelle Ann, 1975-. “Benzo(a)pyrene-mediated effects on cellular adhesion and signal transduction pathways in endometrial cancer.” 2001. Thesis, University of Florida. Accessed April 22, 2021. https://ufdc.ufl.edu/AA00022176.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

McGarry, Michelle Ann, 1975-. “Benzo(a)pyrene-mediated effects on cellular adhesion and signal transduction pathways in endometrial cancer.” 2001. Web. 22 Apr 2021.

Vancouver:

McGarry, Michelle Ann 1. Benzo(a)pyrene-mediated effects on cellular adhesion and signal transduction pathways in endometrial cancer. [Internet] [Thesis]. University of Florida; 2001. [cited 2021 Apr 22]. Available from: https://ufdc.ufl.edu/AA00022176.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

McGarry, Michelle Ann 1. Benzo(a)pyrene-mediated effects on cellular adhesion and signal transduction pathways in endometrial cancer. [Thesis]. University of Florida; 2001. Available from: https://ufdc.ufl.edu/AA00022176

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Florida

4. Shi, Yujiang, 1968-. The Biological function of pinin/DRS/memA and its involvement in tumorigenesis.

Degree: 2000, University of Florida

URL: https://ufdc.ufl.edu/AA00054632

Subjects/Keywords: Cadherins; Cancer; Cell adhesion; Cell growth; Cells; Desmoplakins; Desmosomes; Epithelial cells; Epithelium; Tumors; Cell Adhesion Molecules ( mesh ); Cell Cycle ( mesh ); Cell Nucleus – chemistry ( mesh ); Chromosome Mapping ( mesh ); Chromosomes, Human, Pair 14 ( mesh ); Department of Anatomy and Cell Biology thesis Ph.D ( mesh ); Desmosomes – chemistry ( mesh ); Epithelial Cells ( mesh ); Gene Expression Regulation ( mesh ); Genes, Tumor Suppressor ( mesh ); Neoplasms – genetics ( mesh ); Phosphoproteins ( mesh ); Research ( mesh )

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Shi, Yujiang, 1. (2000). The Biological function of pinin/DRS/memA and its involvement in tumorigenesis. (Thesis). University of Florida. Retrieved from https://ufdc.ufl.edu/AA00054632

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Shi, Yujiang, 1968-. “The Biological function of pinin/DRS/memA and its involvement in tumorigenesis.” 2000. Thesis, University of Florida. Accessed April 22, 2021. https://ufdc.ufl.edu/AA00054632.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Shi, Yujiang, 1968-. “The Biological function of pinin/DRS/memA and its involvement in tumorigenesis.” 2000. Web. 22 Apr 2021.

Vancouver:

Shi, Yujiang 1. The Biological function of pinin/DRS/memA and its involvement in tumorigenesis. [Internet] [Thesis]. University of Florida; 2000. [cited 2021 Apr 22]. Available from: https://ufdc.ufl.edu/AA00054632.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Shi, Yujiang 1. The Biological function of pinin/DRS/memA and its involvement in tumorigenesis. [Thesis]. University of Florida; 2000. Available from: https://ufdc.ufl.edu/AA00054632

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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