UNIVERSITY GRADUATE SCHOOL BULLETIN

ANNOUNCEMENT

Florida International University

University Graduate School

Master’s Thesis Defense

Abstract

Identification of Genes Downstream of Endothelin-3 Signaling: Characterization of WSB1 and SPC12

by

Aniveny Ayala

Hirschsprung disease is a congenital disease characterized by lack of enteric ganglia and abnormal pigmentation pattern indicating that the normal development of melanocytes (pigment producing cells) and enteric neurons has been altered. When the loci of genes mutated in Hirschsprung disease cases were identified, a new door for research was opened. Mutations in the loci coding for Endothelin-3 (Edn3) and its receptor, endothelin receptor B (EdnrB) have since been held responsible for the aberrant phenotype and the signaling cascade they trigger considered essential for the proper development of the neural crest derivatives affected: melanocytes and enteric neurons. Many studies have demonstrated that Edn3/EdnrB signaling is indispensable for melanocyte and enteric neuron development and migration. However, there has not been any research directed to investigate the downstream targets of Edn3/EdnrB signaling. It is therefore the purpose of this study to identify and characterize genes that are transcriptionally regulated by the biochemical pathway that Edn3 signaling elicits.

Data from Differential Display PCR of Edn-3 induced cDNA vs. non-induced cDNA obtained from primary neural crest cultures was analyzed. Bands that clearly show upregulation or downregulation after induction of Edn-3 were sequenced and blasted. Among my results I found WSB1 (a member of the SOCS family of proteins) and the smallest subunit (12kDa) of mammalian signal peptidase.

Using in-situ hybridization, characterization of both genes is presented in this study as well as possible roles in murine development.

Date: November 27, 2001	Department: Biological Sciences
Time: 1:00 p.m.	Major Professor: Dr. Lidia Kos
Place: WC-130