2000 — 2004 |
Bradley, Roger |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
The Role of Protocadherins in Vertebrate Neurogenesis @ Montana State University
0077235 Bradley
During embryonic development, cells destined to develop into discrete tissues must recognize and adhere to one another. These adhesive events are mediate by proteins found on the surfaces of cells, on such family of which are the protocadherins. Recently a novel protocadherin member, termed NFPC, was isolated from the frog, Xenopus laevis. NFP is found in the developing frog nervous system in a subset of neurons in both the spinal cord and eye, implying that NFPC might mediate the adhesion and segregation of these neurons during development. Accordingly this study will dissect the role of NFPC in the adhesive events responsible for correct development of these neurons. As it is not known how protocadherins function as cell adhesion molecules, and whether they may have additional roles in cell signaling, the mechanism by which NFPC acdts will be investigated by isolating and analyzing the cytoplasmic factors with which it interadcts. Finally the roles of other novel protocadherins in vertebrate neural development will be assessed. Results from these studies will provide insights into the molecular mechanisms by which the vertebrate nervous system forms, as well as an elucidation of how protocadherins contribute to this process. Thus, these studies will lead to a better understanding of how alterations in cell adhesion can contribute to the etiology of neural defects and cancer.
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2001 — 2003 |
Copie, Valerie (co-PI) [⬀] Lefcort, Frances [⬀] Bradley, Roger Pierce, Daniel Paden, Charles |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
A Core Equipment Facility For Cellular and Molecular Neuroscience @ Montana State University
This award provides support for purchase of equipment to be used to establish a multi-user, integrated core equipment facility for cellular and molecular biological research. The equipment includes centrifuges, a microinjection apparatus, a spectrophotomer and an inverted microscope. The facility will be shared by faculty in two departments: a newly formed Department of Cell Biology and Neuroscience and an existing Department of Chemistry and Biochemistry. A shared focus of all these investigators is the elucidation of the cellular and molecular mechanisms underlying neural development and/or nerve regeneration. All are now physically located in adjacent labs, and given the overlap in their research methodologies, will be able to share the equipment supported through this award.. Some of the major equipment items requested would replace existing items that are close to 25 years old and in serious disrepair, while others will provide new or expanded capabilities. All major users are members of the NSF sponsored IGERT doctoral training program at the University. This program in Complex Biological Systems is designed to train graduate students to approach biological problems from a multitude of levels, from the molecular to the systems level, using a variety of approaches drawn from cellular and molecular biology, structural biology, computational biology and systems neuroscience. Thus the IGERT trainees will benefit considerably from access to the equipment which will be used in both course work and in thesis research. The equipment will also be available for use by a number of undergraduate students who undertake independent research projects as part of their education.
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2004 — 2007 |
Bradley, Roger S |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Mt Cobre: Nf Protocadherin in Vertebrate Neurogenesis |
0.946 |
2004 — 2009 |
Bradley, Roger |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
The Role of Nf-Protocadherin in Vertebrate Neurulation @ Montana State University
The formation of the embryonic nervous system is a crucial early event in vertebrate development. The process by which the nervous system forms is complex, beginning with the induction of the neural epithelium to form the neural plate, to the subsequent curling and fusion of the neural folds into the neural tube. Key to the process of neurulation are the coordinated cell shape changes and cell movements that occur in the neural plate and neural folds. Amongst the molecules thought to be involved in regulating these cell-cell interactions are members of the cadherin family of cell adhesion molecules. Recently, a new family of cadherin-like genes, the protocadherins, has been isolated, but whose functions during development are generally unknown. At least some protocadherins can function as cell adhesion molecules, and many are expressed in the early nervous system. Thus an important question is whether protocadherins function to mediate cell adhesion during vertebrate neurulation.
This study proposes an in depth analysis of one such protocadherin, NF-protocadherin (NFPC), isolated from Xenopus. NFPC exhibits a striking expression pattern in the early embryonic nervous system, where it is initially restricted to the tips of the neural folds. Furthermore, the cellular protein TAF1, previously shown to interact with NFPC, is also expressed in the neural folds and neural plate, albeit in a broader domain than NFPC. This suggests a role for NFPC and TAF1 in mediating the adhesive events that lead to the formation and/or closing of the neural tube. Accordingly, to dissect the roles of NFPC and TAF1 in neurulation, we propose to disrupt NFPC and TAF1 expression in early embryos, using an antisense morpholino approach, and assess the consequences to neural tube formation. Furthermore, as it is not known how protocadherins function as cell adhesion molecules, and whether they may have additional roles in cell signaling, the mechanism by which NFPC acts will be investigated by isolating and analyzing other cytoplasmic factors with which it interacts.
The results from these studies will provide broader insights into the molecular mechanisms by which the vertebrate nervous system forms, as well as an understanding of how protocadherins contribute to this process. These studies will also lead to elucidation of the intracellular proteins that interact with protocadherins, providing valuable information into how the adhesion between neighboring cells is translated into cellular differentiation and tissue histogenesis. These studies will impact the education and training of students at Montana State University, as both undergraduate and graduate students will be integrally involved in the described projects. Furthermore, many of the techniques utilized in this proposal, such as the injection of RNA and antisense morpholinos into frog embryos, and the analysis of their effect on development, are currently being adapted for use by undergraduates in the Vertebrate Embryology Lab at Montana State University. This in turn will help to train future scientists in the processes, methods and technologies of modern cell and developmental biology.
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2009 — 2012 |
Bradley, Roger |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Protocadherin-Mediated Neural Crest Cell Sorting in the Developing Pns @ Montana State University
Neural crest cells are a multipotent group of cells that contribute to many different organ systems in vertebrates. These cells originate in the developing central nervous system (brain and spinal cord), but then migrate throughout the body to form a variety of tissues, including most of the skull bones, portions of the heart, and the majority of the peripheral nervous system (PNS). A central question in developmental biology is how neural crest cells recognize one another after migration, to then develop into this diverse array of tissues. Using both a biochemical and cell biology approach, this project will study the role of protocadherin-1 (Pcdh1), a member of the cadherin family of cell-cell adhesion molecules, during PNS formation in the chicken embryo. The hypothesis is that Pcdh1 functions as a cell-cell adhesion molecule to mediate the sorting and aggregation of neural crest cells as they form the PNS. To test this hypothesis, the ability of Pcdh1 to mediate cell-cell adhesion will be examined using in vitro aggregation and adhesion assays, as well as by isolating and identifying the cellular proteins that interact with Pcdh1 during cell adhesion.
The results from these studies will provide insights into the mechanisms by which the PNS forms in vertebrates, as well as an understanding of how protocadherins contribute to the process by which neural crest cells sort within the developing embryo. These studies will also greatly impact the education and training of students at Montana State University, as both undergraduate and graduate students will be integrally involved in all aspects of this project. This in turn will help train future scientists in the processes, methods and technologies of modern cell and developmental biology.
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