Isoform requirement of clustered protocadherin for preventing neuronal apoptosis and neonatal lethality
Summary: Clustered protocadherin is a family of cell-surface recognition molecules implicated in neuronal connectivity that has a diverse isoform repertoire and homophilic binding specificity. Mice have 58 isoforms, encoded by Pcdhα, β, and γ gene clusters, and mutant mice lacking all isoforms died...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-01-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222020399 |
| _version_ | 1797946178706341888 |
|---|---|
| author | Hiroaki Kobayashi Kenji Takemoto Makoto Sanbo Masumi Hirabayashi Takahiro Hirabayashi Teruyoshi Hirayama Hiroshi Kiyonari Takaya Abe Takeshi Yagi |
| author_facet | Hiroaki Kobayashi Kenji Takemoto Makoto Sanbo Masumi Hirabayashi Takahiro Hirabayashi Teruyoshi Hirayama Hiroshi Kiyonari Takaya Abe Takeshi Yagi |
| author_sort | Hiroaki Kobayashi |
| collection | DOAJ |
| description | Summary: Clustered protocadherin is a family of cell-surface recognition molecules implicated in neuronal connectivity that has a diverse isoform repertoire and homophilic binding specificity. Mice have 58 isoforms, encoded by Pcdhα, β, and γ gene clusters, and mutant mice lacking all isoforms died after birth, displaying massive neuronal apoptosis and synapse loss. The current hypothesis is that the three specific γC-type isoforms, especially γC4, are essential for the phenotype, raising the question about the necessity of isoform diversity. We generated TC mutant mice that expressed the three γC-type isoforms but lacked all the other 55 isoforms. The TC mutants died immediately after birth, showing massive neuronal death, and γC3 or γC4 expression did not prevent apoptosis. Restoring the α- and β-clusters with the three γC alleles rescued the phenotype, suggesting that along with the three γC-type isoforms, other isoforms are also required for the survival of neurons and individual mice. |
| first_indexed | 2024-04-10T21:06:47Z |
| format | Article |
| id | doaj.art-a7d43fdbc78444aebee00075066854fa |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T21:06:47Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-a7d43fdbc78444aebee00075066854fa2023-01-22T04:40:50ZengElsevieriScience2589-00422023-01-01261105766Isoform requirement of clustered protocadherin for preventing neuronal apoptosis and neonatal lethalityHiroaki Kobayashi0Kenji Takemoto1Makoto Sanbo2Masumi Hirabayashi3Takahiro Hirabayashi4Teruyoshi Hirayama5Hiroshi Kiyonari6Takaya Abe7Takeshi Yagi8KOKORO-Biology Group, Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan; Division of Biophysical Engineering, Department of Systems Science, School of Engineering Science, Osaka University, Toyonaka 565-8531, JapanKOKORO-Biology Group, Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, JapanSection of Mammalian Transgenesis, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki 444-8585, JapanSection of Mammalian Transgenesis, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki 444-8585, JapanKOKORO-Biology Group, Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, JapanKOKORO-Biology Group, Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan; Department of Anatomy and Developmental Neurobiology, Tokushima University, Graduate School of Medical Science, Tokushima 770-8503, JapanLaboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe 6500047, JapanLaboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe 6500047, JapanKOKORO-Biology Group, Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan; Division of Biophysical Engineering, Department of Systems Science, School of Engineering Science, Osaka University, Toyonaka 565-8531, Japan; Corresponding authorSummary: Clustered protocadherin is a family of cell-surface recognition molecules implicated in neuronal connectivity that has a diverse isoform repertoire and homophilic binding specificity. Mice have 58 isoforms, encoded by Pcdhα, β, and γ gene clusters, and mutant mice lacking all isoforms died after birth, displaying massive neuronal apoptosis and synapse loss. The current hypothesis is that the three specific γC-type isoforms, especially γC4, are essential for the phenotype, raising the question about the necessity of isoform diversity. We generated TC mutant mice that expressed the three γC-type isoforms but lacked all the other 55 isoforms. The TC mutants died immediately after birth, showing massive neuronal death, and γC3 or γC4 expression did not prevent apoptosis. Restoring the α- and β-clusters with the three γC alleles rescued the phenotype, suggesting that along with the three γC-type isoforms, other isoforms are also required for the survival of neurons and individual mice.http://www.sciencedirect.com/science/article/pii/S2589004222020399Cell biologyDevelopmental geneticsNeuroscience |
| spellingShingle | Hiroaki Kobayashi Kenji Takemoto Makoto Sanbo Masumi Hirabayashi Takahiro Hirabayashi Teruyoshi Hirayama Hiroshi Kiyonari Takaya Abe Takeshi Yagi Isoform requirement of clustered protocadherin for preventing neuronal apoptosis and neonatal lethality iScience Cell biology Developmental genetics Neuroscience |
| title | Isoform requirement of clustered protocadherin for preventing neuronal apoptosis and neonatal lethality |
| title_full | Isoform requirement of clustered protocadherin for preventing neuronal apoptosis and neonatal lethality |
| title_fullStr | Isoform requirement of clustered protocadherin for preventing neuronal apoptosis and neonatal lethality |
| title_full_unstemmed | Isoform requirement of clustered protocadherin for preventing neuronal apoptosis and neonatal lethality |
| title_short | Isoform requirement of clustered protocadherin for preventing neuronal apoptosis and neonatal lethality |
| title_sort | isoform requirement of clustered protocadherin for preventing neuronal apoptosis and neonatal lethality |
| topic | Cell biology Developmental genetics Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222020399 |
| work_keys_str_mv | AT hiroakikobayashi isoformrequirementofclusteredprotocadherinforpreventingneuronalapoptosisandneonatallethality AT kenjitakemoto isoformrequirementofclusteredprotocadherinforpreventingneuronalapoptosisandneonatallethality AT makotosanbo isoformrequirementofclusteredprotocadherinforpreventingneuronalapoptosisandneonatallethality AT masumihirabayashi isoformrequirementofclusteredprotocadherinforpreventingneuronalapoptosisandneonatallethality AT takahirohirabayashi isoformrequirementofclusteredprotocadherinforpreventingneuronalapoptosisandneonatallethality AT teruyoshihirayama isoformrequirementofclusteredprotocadherinforpreventingneuronalapoptosisandneonatallethality AT hiroshikiyonari isoformrequirementofclusteredprotocadherinforpreventingneuronalapoptosisandneonatallethality AT takayaabe isoformrequirementofclusteredprotocadherinforpreventingneuronalapoptosisandneonatallethality AT takeshiyagi isoformrequirementofclusteredprotocadherinforpreventingneuronalapoptosisandneonatallethality |