First Author | Hasegawa S | Year | 2016 |
Journal | Front Mol Neurosci | Volume | 9 |
Pages | 155 | PubMed ID | 28066179 |
Mgi Jnum | J:244163 | Mgi Id | MGI:5912942 |
Doi | 10.3389/fnmol.2016.00155 | Citation | Hasegawa S, et al. (2016) Distinct and Cooperative Functions for the Protocadherin-alpha, -beta and -gamma Clusters in Neuronal Survival and Axon Targeting. Front Mol Neurosci 9:155 |
abstractText | The clustered protocadherin (Pcdh) genes are divided into the Pcdhalpha, Pcdhbeta, and Pcdhgamma clusters. Gene-disruption analyses in mice have revealed the in vivo functions of the Pcdhalpha and Pcdhgamma clusters. However, all Pcdh protein isoforms form combinatorial cis-hetero dimers and enter trans-homophilic interactions. Here we addressed distinct and cooperative functions in the Pcdh clusters by generating six cluster-deletion mutants (Deltaalpha, Deltabeta, Deltagamma, Deltaalphabeta, Deltabetagamma, and Deltaalphabetagamma) and comparing their phenotypes: Deltaalpha, Deltabeta, and Deltaalphabeta mutants were viable and fertile; Deltagamma mutants lived less than 12 h; and Deltabetagamma and Deltaalphabetagamma mutants died shortly after birth. The Pcdhalpha, Pcdhbeta, and Pcdhgamma clusters were individually and cooperatively important in olfactory-axon targeting and spinal-cord neuron survival. Neurodegeneration was most severe in Deltaalphabetagamma mutants, indicating that Pcdhalpha and Pcdhbeta function cooperatively for neuronal survival. The Pcdhalpha, Pcdhbeta, and Pcdhgamma clusters share roles in olfactory-axon targeting and neuronal survival, although to different degrees. |