Skip to main content
Top
Published in: Brain Structure and Function 1/2019

Open Access 01-01-2019 | Original Article

Cadherin 8 regulates proliferation of cortical interneuron progenitors

Authors: Fani Memi, Abigail C. Killen, Melissa Barber, John G. Parnavelas, William D. Andrews

Published in: Brain Structure and Function | Issue 1/2019

Login to get access

Abstract

Cortical interneurons are born in the ventral forebrain and migrate tangentially in two streams at the levels of the intermediate zone (IZ) and the pre-plate/marginal zone to the developing cortex where they switch to radial migration before settling in their final positions in the cortical plate. In a previous attempt to identify the molecules that regulate stream specification, we performed transcriptomic analysis of GFP-labelled interneurons taken from the two migratory streams during corticogenesis. A number of cadherins were found to be expressed differentially, with Cadherin-8 (Cdh8) selectively present in the IZ stream. We verified this expression pattern at the mRNA and protein levels on tissue sections and found approximately half of the interneurons of the IZ expressed Cdh8. Furthermore, this cadherin was also detected in the germinal zones of the subpallium, suggesting that it might be involved not only in the migration of interneurons but also in their generation. Quantitative analysis of cortical interneurons in animals lacking the cadherin at E18.5 revealed a significant increase in their numbers. Subsequent functional in vitro experiments showed that blocking Cdh8 function led to increased cell proliferation, with the opposite results observed with over-expression, supporting its role in interneuron generation.
Literature
go back to reference Alifragis P, Liapi A, Parnavelas JG (2004) Lhx6 regulates the migration of cortical interneurons from the ventral telencephalon but does not specify their GABA phenotype. J Neurosci 24:5643–5648CrossRefPubMedPubMedCentral Alifragis P, Liapi A, Parnavelas JG (2004) Lhx6 regulates the migration of cortical interneurons from the ventral telencephalon but does not specify their GABA phenotype. J Neurosci 24:5643–5648CrossRefPubMedPubMedCentral
go back to reference Anderson SA, Eisenstat DD, Shi L, Rubenstein JL (1997) Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Science 278:474–476CrossRefPubMed Anderson SA, Eisenstat DD, Shi L, Rubenstein JL (1997) Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Science 278:474–476CrossRefPubMed
go back to reference Benes FM, Berretta S (2001) GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology 25:1–27CrossRefPubMed Benes FM, Berretta S (2001) GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology 25:1–27CrossRefPubMed
go back to reference Cavanagh JF, Mione MC, Pappas IS, Parnavelas JG (1997) Basic fibroblast growth factor prolongs the proliferation of rat cortical progenitor cells in vitro without altering their cell cycle parameters. Cereb Cortex 7:293–302CrossRefPubMed Cavanagh JF, Mione MC, Pappas IS, Parnavelas JG (1997) Basic fibroblast growth factor prolongs the proliferation of rat cortical progenitor cells in vitro without altering their cell cycle parameters. Cereb Cortex 7:293–302CrossRefPubMed
go back to reference Garel S, Garcia-Dominguez M, Charnay P (2000) Control of the migratory pathway of facial branchiomotor neurones. Development 127:5297–5307PubMed Garel S, Garcia-Dominguez M, Charnay P (2000) Control of the migratory pathway of facial branchiomotor neurones. Development 127:5297–5307PubMed
go back to reference Inoue T, Tanaka T, Takeichi M, Chisaka O, Nakamura S, Osumi N (2001) Role of cadherins in maintaining the compartment boundary between the cortex and striatum during development. Development 128:561–569PubMed Inoue T, Tanaka T, Takeichi M, Chisaka O, Nakamura S, Osumi N (2001) Role of cadherins in maintaining the compartment boundary between the cortex and striatum during development. Development 128:561–569PubMed
go back to reference Kido M, Obata S, Tanihara H, Rochelle JM, Seldin MF, Taketani S, Suzuki ST (1998) Molecular properties and chromosomal location of cadherin-8. Genomics 48:186–194CrossRefPubMed Kido M, Obata S, Tanihara H, Rochelle JM, Seldin MF, Taketani S, Suzuki ST (1998) Molecular properties and chromosomal location of cadherin-8. Genomics 48:186–194CrossRefPubMed
go back to reference Korematsu K, Redies C (1997a) Expression of cadherin-8 mRNA in the developing mouse central nervous system. J Comp Neurol 387:291–306CrossRefPubMed Korematsu K, Redies C (1997a) Expression of cadherin-8 mRNA in the developing mouse central nervous system. J Comp Neurol 387:291–306CrossRefPubMed
go back to reference Korematsu K, Redies C (1997b) Restricted expression of cadherin-8 in segmental and functional subdivisions of the embryonic mouse brain. Dev Dyn 208:178–189CrossRefPubMed Korematsu K, Redies C (1997b) Restricted expression of cadherin-8 in segmental and functional subdivisions of the embryonic mouse brain. Dev Dyn 208:178–189CrossRefPubMed
go back to reference Korematsu K, Goto S, Okamura A, Ushio Y (1998a) Heterogeneity of cadherin-8 expression in the neonatal rat striatum: comparison with striatal compartments. Exp Neurol 154:531–536CrossRefPubMed Korematsu K, Goto S, Okamura A, Ushio Y (1998a) Heterogeneity of cadherin-8 expression in the neonatal rat striatum: comparison with striatal compartments. Exp Neurol 154:531–536CrossRefPubMed
go back to reference Korematsu K, Nishi T, Okamura A, Goto S, Morioka M, Hamada J, Ushio Y (1998b) Cadherin-8 protein expression in gray matter structures and nerve fibers of the neonatal and adult mouse brain. Neuroscience 87:303–315CrossRefPubMed Korematsu K, Nishi T, Okamura A, Goto S, Morioka M, Hamada J, Ushio Y (1998b) Cadherin-8 protein expression in gray matter structures and nerve fibers of the neonatal and adult mouse brain. Neuroscience 87:303–315CrossRefPubMed
go back to reference Kuwako K, Nishimoto Y, Kawase S, Okano HJ, Okano H (2014) Cadherin-7 regulates mossy fiber connectivity in the cerebellum. Cell Rep 9:311–323CrossRefPubMed Kuwako K, Nishimoto Y, Kawase S, Okano HJ, Okano H (2014) Cadherin-7 regulates mossy fiber connectivity in the cerebellum. Cell Rep 9:311–323CrossRefPubMed
go back to reference Lefkovics K, Mayer M, Bercsenyi K, Szabo G, Lele Z (2012) Comparative analysis of type II classic cadherin mRNA distribution patterns in the developing and adult mouse somatosensory cortex and hippocampus suggests significant functional redundancy. J Comp Neurol 520:1387–1405. https://doi.org/10.1002/cne.22801 CrossRefPubMed Lefkovics K, Mayer M, Bercsenyi K, Szabo G, Lele Z (2012) Comparative analysis of type II classic cadherin mRNA distribution patterns in the developing and adult mouse somatosensory cortex and hippocampus suggests significant functional redundancy. J Comp Neurol 520:1387–1405. https://​doi.​org/​10.​1002/​cne.​22801 CrossRefPubMed
go back to reference Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 25:402–408CrossRefPubMed Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 25:402–408CrossRefPubMed
go back to reference Lu Y, Lemon W, Liu PY, Yi YJ, Morrison C, Yang P, Sun ZF, Szoke J, Gerald WL, Watson M, Govindan R, You M (2006) A gene expression signature predicts survival of patients with stage I non-small cell lung cancer. PLoS Med 3:2229–2243CrossRef Lu Y, Lemon W, Liu PY, Yi YJ, Morrison C, Yang P, Sun ZF, Szoke J, Gerald WL, Watson M, Govindan R, You M (2006) A gene expression signature predicts survival of patients with stage I non-small cell lung cancer. PLoS Med 3:2229–2243CrossRef
go back to reference Manabe T, Togashi H, Uchida N, Suzuki SC, Hayakawa Y, Yamamoto M, Yoda H, Miyakawa T, Takeichi M, Chisaka O (2000) Loss of cadherin-11 adhesion receptor enhances plastic changes in hippocampal synapses and modifies behavioral responses. Mol Cel Neurosci 15:534–546. https://doi.org/10.1006/mcne.2000.0849 CrossRef Manabe T, Togashi H, Uchida N, Suzuki SC, Hayakawa Y, Yamamoto M, Yoda H, Miyakawa T, Takeichi M, Chisaka O (2000) Loss of cadherin-11 adhesion receptor enhances plastic changes in hippocampal synapses and modifies behavioral responses. Mol Cel Neurosci 15:534–546. https://​doi.​org/​10.​1006/​mcne.​2000.​0849 CrossRef
go back to reference Medina L, Legaz I, Gonzalez G, De Castro F, Rubenstein JL, Puelles L (2004) Expression of Dbx1, Neurogenin 2, Semaphorin 5A, Cadherin 8, and Emx1 distinguish ventral and lateral pallial histogenetic divisions in the developing mouse claustroamygdaloid complex. J Comp Neurol 474:504–523CrossRefPubMed Medina L, Legaz I, Gonzalez G, De Castro F, Rubenstein JL, Puelles L (2004) Expression of Dbx1, Neurogenin 2, Semaphorin 5A, Cadherin 8, and Emx1 distinguish ventral and lateral pallial histogenetic divisions in the developing mouse claustroamygdaloid complex. J Comp Neurol 474:504–523CrossRefPubMed
go back to reference Nakagawa S, Takeichi M (1998) Neural crest emigration from the neural tube depends on regulated cadherin expression. Development 125:2963–2971PubMed Nakagawa S, Takeichi M (1998) Neural crest emigration from the neural tube depends on regulated cadherin expression. Development 125:2963–2971PubMed
go back to reference Pagnamenta AT, Khan H, Walker S, Gerrelli D, Wing K, Bonaglia MC, Giorda R, Berney T, Mani E, Molteni M, Pinto D, Le Couteur A, Hallmayer J, Sutcliffe JS, Szatmari P, Paterson AD, Scherer SW, Vieland VJ, Monaco AP (2011) Rare familial 16q21 microdeletions under a linkage peak implicate cadherin 8 (CDH8) in susceptibility to autism and learning disability. J Med Genet 48:48–54. https://doi.org/10.1136/jmg.2010.079426 CrossRefPubMed Pagnamenta AT, Khan H, Walker S, Gerrelli D, Wing K, Bonaglia MC, Giorda R, Berney T, Mani E, Molteni M, Pinto D, Le Couteur A, Hallmayer J, Sutcliffe JS, Szatmari P, Paterson AD, Scherer SW, Vieland VJ, Monaco AP (2011) Rare familial 16q21 microdeletions under a linkage peak implicate cadherin 8 (CDH8) in susceptibility to autism and learning disability. J Med Genet 48:48–54. https://​doi.​org/​10.​1136/​jmg.​2010.​079426 CrossRefPubMed
go back to reference Sawada G, Ueo H, Matsumura T, Uchi R, Ishibashi M, Mima K, Kurashige J, Takahashi Y, Akiyoshi S, Sudo T, Sugimachi K, Doki Y, Mori M, Mimori K (2013) CHD8 is an independent prognostic indicator that regulates Wnt/β-catenin signaling and the cell cycle in gastric cancer. Oncol Rep 30:1137–1142. https://doi.org/10.3892/or.2013.2597 CrossRefPubMed Sawada G, Ueo H, Matsumura T, Uchi R, Ishibashi M, Mima K, Kurashige J, Takahashi Y, Akiyoshi S, Sudo T, Sugimachi K, Doki Y, Mori M, Mimori K (2013) CHD8 is an independent prognostic indicator that regulates Wnt/β-catenin signaling and the cell cycle in gastric cancer. Oncol Rep 30:1137–1142. https://​doi.​org/​10.​3892/​or.​2013.​2597 CrossRefPubMed
go back to reference Suzuki SC, Furue H, Koga K, Jiang N, Nohmi M, Shimazaki Y, Katoh-Fukui Y, Yokoyama M, Yoshimura M, Takeichi M (2007) Cadherin-8 is required for the first relay synapses to receive functional inputs from primary sensory afferents for cold sensation. J Neurosci 27:3466–3476CrossRefPubMedPubMedCentral Suzuki SC, Furue H, Koga K, Jiang N, Nohmi M, Shimazaki Y, Katoh-Fukui Y, Yokoyama M, Yoshimura M, Takeichi M (2007) Cadherin-8 is required for the first relay synapses to receive functional inputs from primary sensory afferents for cold sensation. J Neurosci 27:3466–3476CrossRefPubMedPubMedCentral
go back to reference Takeichi M (2007) The cadherin superfamily in neuronal connections and interactions. Nat Rev Neurosci 8:11–20CrossRefPubMed Takeichi M (2007) The cadherin superfamily in neuronal connections and interactions. Nat Rev Neurosci 8:11–20CrossRefPubMed
go back to reference Tamamaki N, Yanagawa Y, Tomioka R, Miyazaki J, Obata K, Kaneko T (2003) Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67-GFP knock-in mouse. J Comp Neurol 467:60–79CrossRefPubMed Tamamaki N, Yanagawa Y, Tomioka R, Miyazaki J, Obata K, Kaneko T (2003) Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67-GFP knock-in mouse. J Comp Neurol 467:60–79CrossRefPubMed
go back to reference Taniguchi H, Kawauchi D, Nishida K, Murakami F (2006) Classic cadherins regulate tangential migration of precerebellar neurons in the caudal hindbrain. Development 133:1923–1931CrossRefPubMed Taniguchi H, Kawauchi D, Nishida K, Murakami F (2006) Classic cadherins regulate tangential migration of precerebellar neurons in the caudal hindbrain. Development 133:1923–1931CrossRefPubMed
go back to reference Thomaidou D, Mione MC, Cavanagh JF, Parnavelas JG (1997) Apoptosis and its relation to the cell cycle in the developing cerebral cortex. J Neurosci 17:1075–1085CrossRefPubMedPubMedCentral Thomaidou D, Mione MC, Cavanagh JF, Parnavelas JG (1997) Apoptosis and its relation to the cell cycle in the developing cerebral cortex. J Neurosci 17:1075–1085CrossRefPubMedPubMedCentral
go back to reference Treubert-Zimmermann U, Heyers D, Redies C (2002) Targeting axons to specific fiber tracts in vivo by altering cadherin expression. J Neurosci 22:7617–7626CrossRefPubMedPubMedCentral Treubert-Zimmermann U, Heyers D, Redies C (2002) Targeting axons to specific fiber tracts in vivo by altering cadherin expression. J Neurosci 22:7617–7626CrossRefPubMedPubMedCentral
Metadata
Title
Cadherin 8 regulates proliferation of cortical interneuron progenitors
Authors
Fani Memi
Abigail C. Killen
Melissa Barber
John G. Parnavelas
William D. Andrews
Publication date
01-01-2019
Publisher
Springer Berlin Heidelberg
Published in
Brain Structure and Function / Issue 1/2019
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-018-1772-4

Other articles of this Issue 1/2019

Brain Structure and Function 1/2019 Go to the issue