A Transcriptome Atlas of the Developing Mouse Urogenital System

Rathi Thiagarajan (2011). A Transcriptome Atlas of the Developing Mouse Urogenital System PhD Thesis, Institute for Molecular Bioscience, The University of Queensland.

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Author Rathi Thiagarajan
Thesis Title A Transcriptome Atlas of the Developing Mouse Urogenital System
School, Centre or Institute Institute for Molecular Bioscience
Institution The University of Queensland
Publication date 2011-05
Thesis type PhD Thesis
Supervisor Prof. Sean M Grimmond
Prof. Melissa H Little
Total pages 113
Total colour pages 30
Total black and white pages 83
Language eng
Subjects 06 Biological Sciences
Abstract/Summary Organ development is a complex process which involves precise orchestration of multiple cell types across time and space. Understanding of urogenital organ development has benefited from the use of mouse models, as it is ideal for laboratory-based genetic manipulations. Recent advances in highthroughput strategies and genomic technologies have enabled global surveys of the transcriptome, and improved characterization of dynamic gene expression states. Such resources can be used to compile gene expression atlases to obtain information of mRNA levels and localization as a basis to understand cellular fate-decision pathways and networks during development. This thesis describes the temporal and spatial transcriptome atlas of the developing mouse urogenital system, with emphasis on the renal system, as a resource to study the cellular and molecular blueprint required for organogenesis. The analyses that encompass this atlas relied heavily upon resources from the GenitoUrinary Development Molecular Anatomy Project (GUDMAP) from which this thesis stems from. The underlying foundation of this atlas provides the basis to understand what is encoded in the transcriptome during organ development. What are the genes required for dynamic regulation of organ development? What cell-types do they represent? How is their expression controlled? And how do these genes and their transcriptional structure encode the instructions to build complex, multi-cellular organs. The first results chapter describes the integration of microarray profiling to identify genome-wide temporal and spatial markers of ovary and testis during gonad development accompanied by in situ hybridization to validate expression and capture the domain-specific expression patterns exhibited by these genes. The second chapter presents a high-resolution investigation of 11 embryonic kidney subcompartment-specific genes which revealed additional molecularly-defined compartments specific cell types within complex heterogeneous compartments. These ‘anchor genes’ formed the basis to model gene expression networks during tissue ligand-receptor interactions and transcription factors regulating tissue specific expression. The final chapter sets the scene for the next phase of analyses towards the survey of transcriptional complexity driving temporal and spatial regulation of gene expression programs in the embryonic kidney using RNA-sequencing. This study provided the basis to update current gene models of developmental programs to include transcriptional dynamics regulating these processes. Together, the outcomes of this thesis provide a valuable resource of genetic markers that can be formally used for cell lineage tracing to map the fate of each cell type in the developmental history of the genitourinary system and facilitate functional studies through transgenic tools. The transcriptome atlas forms a comprehensive dynamic survey of the developing mouse urogenital system, and represents an important resource for functional studies into organ development which will ultimately lead to strategies for tissue regeneration to treat organ damage and disease.
Keyword Transcriptome, gene expression, kidney, gonad, ovaries, testis, organogenesis, microarray, RNA-Seq, next-generation sequencing
Additional Notes colour: 15, 17, 20, 22, 26, 33, 38, 40, 43, 50, 52, 54, 56, 57, 59, 68, 69, 70, 72, 74, 75, 76, 81, 83, 84, 86, 87, 88, 89, 90. landscape: 33.

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Created: Thu, 09 Feb 2012, 17:15:15 EST by Ms Rathi Thiagarajan on behalf of Library - Information Access Service