Characterization of a Single Genomic Locus Encoding the Clustered Protocadherin Receptor Diversity in Xenopus tropicalis.
Clustered protocadherins (cPcdhs) constitute the largest subgroup of the cadherin superfamily, and in mammals are grouped into clusters of α-, β-, and γ-types. Tens of tandemly arranged paralogous Pcdh genes of the Pcdh clusters generate a substantial diversity of receptor isoforms. cPcdhs are known to have important roles in neuronal development, and genetic alterations of cPcdhs have been found to be associated with several neurological diseases. Here, we present a first characterization of cPcdhs in Xenopus tropicalis We determined and annotated all cPcdh isoforms, revealing that they are present in a single chromosomal locus. We validated a total of 96 isoforms, which we show are organized in three distinct clusters. The X. tropicalis cPcdh locus is composed of one α- and two distinct γ-Pcdh clusters (pcdh-γ1 and pcdh-γ2). Bioinformatics analyses assisted by genomic BAC clone sequencing showed that the X. tropicalis α- and γ-Pcdhs are conserved at the cluster level, but, unlike mammals, X. tropicalis does not contain a β-Pcdh cluster. In contrast, the number of γ-Pcdh isoforms has expanded, possibly due to lineage-specific gene duplications. Interestingly, the number of X. tropicalis α-Pcdhs is identical between X. tropicalis and mouse. Moreover, we find highly conserved as well as novel promoter elements potentially involved in regulating the cluster-specific expression of cPcdh isoforms. This study provides important information for the understanding of the evolutionary history of cPcdh genes and future mechanistic studies. It provides an annotated X. tropicalis cPcdh genomic map and a first molecular characterization essential for functional and comparative studies.
Neuronal Wiring Laboratory, Vlaams Instituut voor Biotechnologie (VIB), University of Leuven, 3000, Belgium Department of Human Genetics, School of Medicine, University of Leuven, 3000 Belgium.
Hakki E
HE
Etlioglu
Laboratory for Functional Genomics and Systems Biology, Berlin Institute for Medical Systems Biology, Max-Delbrück-Centrum für Molekulare Medizin, 13125 Berlin, Germany.
Wei
W
Sun
Neuronal Wiring Laboratory, Vlaams Instituut voor Biotechnologie (VIB), University of Leuven, 3000, Belgium Department of Human Genetics, School of Medicine, University of Leuven, 3000 Belgium.
Zengjin
Z
Huang
Laboratory for Functional Genomics and Systems Biology, Berlin Institute for Medical Systems Biology, Max-Delbrück-Centrum für Molekulare Medizin, 13125 Berlin, Germany wei.chen@mdc-berlin.de dietmar.schmucker@vib-kuleuven.be.
Wei
W
Chen
Neuronal Wiring Laboratory, Vlaams Instituut voor Biotechnologie (VIB), University of Leuven, 3000, Belgium Department of Human Genetics, School of Medicine, University of Leuven, 3000 Belgium wei.chen@mdc-berlin.de dietmar.schmucker@vib-kuleuven.be.
Dietmar
D
Schmucker
D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D015820:Cadherins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D014644:Genetic Variation; D023281:Genomics; D006801:Humans; D051379:Mice; D005810:Multigene Family / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D014981:Xenopus / Q000235:genetics
D015820:Cadherins; D020033:Protein Isoforms
Xenopus tropicalis; gene cluster; neuronal development; protocadherin receptor diversity