Analysis of Endoderm Patterning and Pancreatic Organogenesis in Xenopus laevis

Bilogan, Cassandra K.

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Year:: 2014
Contributor:: Bilogan, Cassandra K (creator); Horb, Marko (Director); Wessel, Gary (Reader); Mowry, Kimberly (Reader); Wharton, Kristi (Reader); He, Xi (Reader); Brown University. BIOMED: Molecular Biology, Cell Biology, and Biochemistry (sponsor)
Genre:: theses
Subject:: Endoderm; Staufen2; Ptf1a; Development; Xenopus; Economic development; Pancreas
Extent:: xiii, 219 p.
DOI: https://doi.org/10.7301/Z0445JVD

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Abstract:: The endoderm germ layer gives rise to the epithelial lining of the respiratory and digestive tracts and their associated organs. Gastrulation and formation of the organizer are essential for proper specification and patterning of all three germ layers, including the endoderm. The organizer expresses transcription factors and secreted proteins to pattern the germ layers; however how the same factors can lead to the specification of all three germ layers is not fully understood. We demonstrated that stau2, a well-conserved dsRBP is expressed throughout the Xenopus embryo at gastrulation and becomes localized to neural tissue and the anterior endoderm at tailbud stages. Targeted knockdown of Stau2 within the development anterior endoderm and mesoderm led to the loss of stomach, liver and pancreas formation. We demonstrated that Stau2 function was required at the onset of gastrulation to maintain expression of Wnt/β-catenin signaling effector proteins and this lead to a reduction in organizer gene expression during gastrulation. RIP-seq of Stau2-bound mRNA targets at the onset of gastrulation led to the identification of many novel targets including gsk3β, a known Wnt signaling inhibitor. We demonstrated that Stau2 function was required during gastrulation for proper patterning of the endoderm. We have identified a phenotype that is initiated during gastrulation whereby only endoderm patterning is affected, providing evidence that the endoderm and mesoderm are patterned beginning separately at the onset of gastrulation. The pancreas is an endodermally derived organ composed of both endocrine and exocrine cells. The bHLH factor Ptf1a is required for proper pancreas development, however how it elicits this function remains unknown. We set out to gain insight into the gene regulatory network activated by Ptf1a in early pancreas development. We isolated anterior endoderm tissue overexpressing Ptf1a at two stages and compared their gene expression profiles using microarrays. Our results revealed that Ptf1a regulates genes with a variety of functions, providing insight into the complex regulatory network required for pancreas specification. A better understanding of the complex regulatory networks required throughout endoderm development would be provide insight into the pathology of endodermal diseases likely leading to more streamline drug discovery.
Notes:: Thesis (Ph.D. -- Brown University (2014)

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Rights: In Copyright
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Bilogan, Cassandra K., "Analysis of Endoderm Patterning and Pancreatic Organogenesis in Xenopus laevis" (2014). Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.7301/Z0445JVD

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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations

Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department.
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