Proteome Dynamics in Neural and Neurosensory Development
Open AccessNeural developmental defects and hearing loss are prevalent in the US. Understanding the mechanisms that regulate neural development is important for advancing health sciences. We need to expand our understanding of the biomolecules that drive and regulate development. To that end, there is now a need to gain complementary information about the proteins and metabolites that may play a role in developing neural and neurosensory systems. Recent advances in mass spectrometry have enabled direct measurements of proteins from biological tissues. The research presented herein highlights the application of high-resolution mass spectrometry to study proteome dynamics towards advancing our understanding of neural development. The first part of the dissertation describes the analytical approaches that were developed and applied to enable proteomic analysis from Xenopus embryos. A novel approach was developed to enable lineage-guided dissection and analysis of neural cells in Xenopus embryos. The next set of studies focuses on analyzing proteins from neural inductive and neural ectodermal cells during gastrulation. We report an elevation in oxidative phosphorylation and the production of reactive oxygen species in the organizer, a transient signaling center that orchestrates dorsal-ventral patterning and neural induction in the adjoining ectoderm. We also show that the differentiation of the embryonic ectoderm to the neural ectoderm, the precursor to the central nervous system, is accompanied by an increase in the production of histone and chromatin regulatory proteins. The final portion of this work focuses on advancing our understanding of hearing loss and improving identification of gene candidates for unexplained cases of hearing loss though studying proteome dynamics during inner ear development. We report an increase in extra cellular matrix proteins during otic morphogenesis. We also identify the gene tgfbi as a potential candidate for syndromic hearing loss. The innovative studies in this work have contributed to the field of developmental neurobiology by providing novel methods, comprehensive information on proteins produced in the embryo, and by highlighting new roles for biomolecules during neural development. Thus, we hope that the results from this work will ultimately help improve the diagnosis and treatment for neural developmental and hearing loss disorders.
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