Posttranscriptional Regulation of the Neurofibromatosis 2 Gene
Abstract
Neurofibromatosis type 2 (NF2) is associated with a homozygous inactivation of the neurofibromatosis 2 (NF2) gene. Despite intense study of the NF2 gene the mechanism by which the NF2 tumor suppressor acts to prevent tumor formation is not well understood. The goal of this research is to examine the role of posttranscriptional regulation of the NF2 gene. During this reporting penod we have confirmed our findings that vestibular schwannomas express a distinct pattern of alternatively spliced NF2 transcripts lacking specific exons. We have carried out a detailed analysis of NF2 expression during embryonic development and in the tissues affected by NF2 using the transgenic in situ hybridization and antibody staining approaches. We show that NF2 promoter expression was detected as early as E5.5. Strong NF2 promoter activity was seen in the embryonic ectoderm and in all NF2-affected tissues examined. Importantly we observed strong NF2 promoter activity in the developing brain and in sites containing migrating cells including the neural tube closure. We also noted a transient change of NF2 promoter activity during neural crest cell migration. While little NF2 promoter expression was detected in premigratory neural crest cells at the dorsal ridge region of the neural fold significant activity was seen in the neural crest cells already migrating away from the dorsal neural tube. The NF2 promoter expression pattern during embryogenesis suggests a specific regulation of the NF2 gene during neural crest cell migration and further support the role of merlin in cell adhesion motility and proliferation during development. By using the conditional gene targeting approach we have created an Nf2floxB allele and are in the process of generating a conditional exon 8 knockout mouse. These transgenic and knockout experiments should allow us to study the function of schwannoma-expressed NF2 isoforms in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2005
- Accession Number
- ADA457830
Entities
People
- Long-Sheng Chang