hox Gene Regulation and Function During Zebrafish Embryogenesis: A Dissertation
Authors
Weicksel, Steven E.Faculty Advisor
Charles Sagerström, PhDAcademic Program
Biochemistry and Molecular PharmacologyUMass Chan Affiliations
Biochemistry and Molecular PharmacologyDocument Type
Doctoral DissertationPublication Date
2013-10-28Keywords
Dissertations, UMMSGenes, Homeobox
Homeodomain Proteins
Zebrafish
Zebrafish Proteins
Embryonic Development
Nucleosomes
Gene Expression Regulation, Developmental
Homeobox Genes
Homeodomain Proteins
Zebrafish
Zebrafish Proteins
Embryonic Development
Nucleosomes
Developmental Gene Expression Regulation
Developmental Biology
Genetics
Genomics
Molecular Genetics
Metadata
Show full item recordAbstract
Hox genes encode a conserved family of homeodomain containing transcription factors essential for metazoan development. The establishment of overlapping Hox expression domains specifies tissue identities along the anterior-posterior axis during early embryogenesis and is regulated by chromatin architecture and retinoic acid (RA). Here we present the role nucleosome positioning plays in hox activation during embryogenesis. Using four stages of early embryo development, we map nucleosome positions at 37 zebrafish hox promoters. We find nucleosome arrangement to be progressive, taking place over several stages independent of RA. This progressive change in nucleosome arrangement on invariant sequence suggests that trans-factors play an important role in organizing nucleosomes. To further test the role of trans-factors, we created hoxb1b and hoxb1a mutants to determine if the loss of either protein effected nucleosome positions at the promoter of a known target, hoxb1a. Characterization of these mutations identified hindbrain segmentation defects similar to targeted deletions of mouse orthologs Hoxa1 and Hoxb1 and zebrafish hoxb1b and hoxb1a morpholino (MO) loss-of-function experiments. However, we also identified differences in hindbrain segmentation as well as phenotypes in facial motor neuron migration and reticulospinal neuron formation not previously observed in the MO experiments. Finally, we find that nucleosomes at the hoxb1a promoter are positioned differently in hoxb1b-/- embryos compared to wild-type. Together, our data provides new insight into the roles of hoxb1b and hoxb1a in zebrafish hindbrain segmentation and reticulospinal neuron formation and indicates that nucleosome positioning at hox promoters is dynamic, depending on sequence specific factors such as Hox proteins.DOI
10.13028/M24G7VPermanent Link to this Item
http://hdl.handle.net/20.500.14038/32048Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/M24G7V
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