Transgenic Expression of Endothelin Receptor-B Rescues the Aganglionosis Phenotype of Piebald Lethal Mice

Neural crest cells (NCC) are a unique population of cells in vertebrates that arise between the presumptive epidermis and the dorsal most region of the neural tube. During neurulation, NCC migrate to many regions of the body to give rise to a wide variety of cell types. NCC that originate from the neural tube at the levels of somite 1-7 colonize the gut and give rise to the enteric ganglia. The endothelin signaling pathway has been shown to be crucial for proper development of some neural crest derivatives. Mice and humans with mutations in the Endothelin receptor b (Ednrb) gene exhibit similar phenotypes characterized by hypopigmentation, hearing loss, and megacolon. Thesephenotypes are due to lack of melanocytes in the skin, inner ear and enteric ganglia in the distal portion of the colon, respectively. It is well established that Ednrb is required early during the embryonic development for normal innervation of the gut. However, it is not clear if Ednrb acts on enteric neuron precursor cells or in pre-committed NC precursors. Additionally, it is controversial whether the action of Ednrb is cell autonomous or non- autonomous. We generated transgenic mice that express Ednrb under the control of the Nestin second intron enhancer (Nes) which drives expression to pre-migrating NCC. These mice were crosses to the spontaneous mouse mutant piebald lethal, which carriers a null mutation in Ednrb and exhibits enteric aganglionosis. The Nes-Ednrb was capable of rescuing the aganglianosis phenotype of piebald lethal mutants demonstrating that expression of Ednrb in pre-committed precursors is sufficient for normal enteric ganglia development. This study provides insight in early embryonic development of NCC and could eventually have potential use in cellular therapies for Hirschsprung's disease.

Optimal kernel development for real-time communications

The purpose of this research is to develop an optimal kernel which would be used in a real-time engineering and communications system. Since the application is a real-time system, relevant real-time issues are studied in conjunction with kernel related issues. The emphasis of the research is the development of a kernel which would not only adhere to the criteria of a real-time environment, namely determinism and performance, but also provide the flexibility and portability associated with non-real-time environments. The essence of the research is to study how the features found in non-real-time systems could be applied to the real-time system in order to generate an optimal kernel which would provide flexibility and architecture independence while maintaining the performance needed by most of the engineering applications. Traditionally, development of real-time kernels has been done using assembly language. By utilizing the powerful constructs of the C language, a real-time kernel was developed which addressed the goals of flexibility and portability while still meeting the real-time criteria. The implementation of the kernel is carried out using the powerful 68010/20/30/40 microprocessor based systems.