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Positional cloning and functional analysis of the SF3B1gene in zebrafish

An, Min
http://rave.ohiolink.edu/etdc/view?acc_num=osu1180528932

Abstract Details

2007, Doctor of Philosophy, Ohio State University, Neuroscience.
Zebrafish toast b460( tst) is a recessive embryonic lethal mutation, characterized by visible defects in both neural crest and blood development. tstis involved in the neural plate border development in zebrafish embryos, resulting in the complete lack neural crest derivatives and a decrease in the number of Rohon-Beard sensory neurons. In addition, lateral plate mesoderm development is also affected in tstmutants, as development of most of its derivatives are disrupted during hematopoiesis, vasculogenesis, and cardiogenesis. Other ectodermal and mesodermal derivatives develop normally in tstmutants. The tstlocus has been positionally cloned and encodes splicing factor 3b subunit 1 ( sf3b1). Sequence analysis between wild-type and homozygous mutant genomic DNA identified the nucleotide mutation at 5′ splicing site in the 4th intron of sf3b1genomic DNA where T is changed to G in the tstmutant gene. The nucleotide change causes abnormal splicing in tsthomozygotes with variant transcripts. The truncations are predicted to occur in the extreme N-terminal region of the protein, thus eliminating essential functional regions and are therefore predicted to be non-functional. The presence of normal transcripts and the more severe phenotype of sf3b1 morphants compared to tstmutants indicate that the tstmutation is hypomorphic. Zebrafish genome analysis shows that sf3b1is a single-copy gene. It is expressed ubiquitously during early embryonic development in zebrafish. Studies of interactions between sf3b1and key transcriptional regulators of neural crest development and hematopoiesis reveal that deficiency of sf3b1function not only causes disruption in the expression levels of genes required for sublineage fate specification, but also results in abnormal pre-mRNA splicing of some of these genes. As a result, the survival, migration, and differentiation of cells derived from both neural plate border and lateral plate mesoderm are severely disrupted. These results demonstrate that the ubiquitous and essential pre-mRNA processing gene sf3b1is required to different degrees by specific embryonic cell populations during development. Thus, while some genes are required by all cell types, the timing and degree of the requirement for such ”housekeeping” genes differs for specific embryonic cell population during embryogenesis.
Paul Henion (Advisor)
149 p.
Biology, Neuroscience
Splicing factor 3b subunit 1 ( sf3b1),; Neural plate border,; Lateral plate mesoderm,; Early embryogenesis; Positional cloning; Zebrafish

Recommended Citations

Citations

  • An, M. (2007). Positional cloning and functional analysis of the SF3B1gene in zebrafish [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1180528932

    APA Style (7th edition)

  • An, Min. Positional cloning and functional analysis of the SF3B1gene in zebrafish. 2007. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1180528932.

    MLA Style (8th edition)

  • An, Min. "Positional cloning and functional analysis of the SF3B1gene in zebrafish." Doctoral dissertation, Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=osu1180528932

    Chicago Manual of Style (17th edition)

osu1180528932
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© 2007, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.