title: Conserved alternative splicing and expression patterns of arthropod N-cadherin.
abstract: Metazoan development requires complex mechanisms to generate cells with diverse function. Alternative splicing of pre-mRNA not only expands proteomic diversity but also provides a means to regulate tissue-specific molecular expression. The N-Cadherin gene in Drosophila contains three pairs of mutually-exclusive alternatively-spliced exons (MEs). However, no significant differences among the resulting protein isoforms have been successfully demonstrated in vivo. Furthermore, while the N-Cadherin gene products exhibit a complex spatiotemporal expression pattern within embryos, its underlying mechanisms and significance remain unknown. Here, we present results that suggest a critical role for alternative splicing in producing a crucial and reproducible complexity in the expression pattern of arthropod N-Cadherin. We demonstrate that the arthropod N-Cadherin gene has maintained the three sets of MEs for over 400 million years using in silico and in vivo approaches. Expression of isoforms derived from these MEs receives precise spatiotemporal control critical during development. Both Drosophila and Tribolium use ME-13a and ME-13b in "neural" and "mesodermal" splice variants, respectively. As proteins, either ME-13a- or ME-13b-containing isoform can cell-autonomously rescue the embryonic lethality caused by genetic loss of N-Cadherin. Ectopic muscle expression of either isoform beyond the time it normally ceases leads to paralysis and lethality. Together, our results offer an example of well-conserved alternative splicing increasing cellular diversity in metazoans.
authors.affiliation: Neuroscience Program, University of Illinois, Urbana, Illinois, United States of America. shuningh@uci.edu
authors.forename: Shu-Ning
authors.initials: SN
authors.lastname: Hsu
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yonekura
authors.forename: Chun-Yuan
authors.initials: CY
authors.lastname: Ting
authors.forename: Hugh M
authors.initials: HM
authors.lastname: Robertson
authors.forename: Youichi
authors.initials: Y
authors.lastname: Iwai
authors.forename: Tadashi
authors.initials: T
authors.lastname: Uemura
authors.forename: Chi-Hon
authors.initials: CH
authors.lastname: Lee
authors.forename: Akira
authors.initials: A
authors.lastname: Chiba