Elucidating the molecular mechanisms that guide and shape the development of nervous systems within the human body is paramount not only from the perspective of developmental biology, but also from a medical viewpoint concerning the palliative and curative treatment of congenital birth defects, as well as for engineering potential treatments for degenerative diseases. Our focus was to first study a relatively simple model of nervous system development and then progress to a more complex system for analysis The sympathetic nervous system (SNS), a subdivision of the peripheral nervous system (PNS), is a relatively simple system to study, particularly the development of the sympathetic chain ganglia (SCG). We sought to discover whether the powerful morphogen sonic hedgehog (Shh) is involved in the migration, patterning, or specification of the developing SNS. Our results indicate that Shh is essential for migration and patterning, but not for neural, glial, or catecholaminergic specification of the SNS We next studied the enteric nervous system (ENS) as a complex model of nervous system development. The ENS is the largest and most complex division of the PNS, containing many striking similarities to the brain. Recently, the basic helix-loop-helix (bHLH) transcription factor Hand2 has been shown to be involved in neuronal phenotype selection in embryos with a neural crest specific deletion of Hand2. Unfortunately, these embryos die due to cardiac defects by 12.5 dpc. By attempting two distinct methods to rescue Hand2 mutant embryos until birth, we were able to successfully analyze how the loss of Hand2 effects the development of the ENS. Our results demonstrate that Hand2 plays a key role in migration, patterning, neuronal and glial specification, as well as neuronal phenotype selection within the developing ENS Together, the studies of these two nervous systems add to the cumulative research and contribute toward the search for a complete understanding of nervous system development that is essential in the treatment of a number of congenital disorders affecting the PNS such as neuroblastoma, Hirschsprung's Disease, hyperganglionosis, and intestinal neuronal displaysia type B, as well as the in treatment of other diseases including hyperthyroidism, heart failure, chronic arterial hypertension, anxiety, and irritable bowel syndrome / acase@tulane.edu
| Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_25720 |
| Date | January 2010 |
| Contributors | Maska, Emily Louise (Author), Schrader, Laura (Thesis advisor) |
| Publisher | Tulane University |
| Source Sets | Tulane University |
| Language | English |
| Detected Language | English |
| Rights | Access requires a license to the Dissertations and Theses (ProQuest) database., Copyright is in accordance with U.S. Copyright law |
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