ApoER2 Controls not only neuronal migration in the intermediate zone but also termination of migration in the developing cerebral cortex

Yuki Hirota, Kenichiro Kubo, Takahiro Fujino, Tokuo T. Yamamoto, Kazunori Nakajima

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Neuronal migration contributes to the establishment of mammalian brain. The extracellular protein Reelin sends signals to various downstream molecules by binding to its receptors, the apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor and exerts essential roles in the neuronal migration and formation of the layered neocortex. However, the cellular and molecular functions of Reelin signaling in the cortical development are not yet fully understood. Here, to gain insight into the role of Reelin signaling during cortical development, we examined the migratory behavior of Apoer2-deficient neurons in the developing brain. Stage-specific labeling of newborn neurons revealed that the neurons ectopically invaded the marginal zone (MZ) and that neuronal migration of both early- and late-born neurons was disrupted in the intermediate zone (IZ) in the Apoer2 KO mice. Rescue experiments showed that ApoER2 functions both in cell-autonomous and noncell-autonomous manners, that Rap1, integrin, and Akt are involved in the termination of migration beneath the MZ, and that Akt also controls neuronal migration in the IZ downstream of ApoER2. These data indicate that ApoER2 controls multiple processes in neuronal migration, including the early stage of radial migration and termination of migration beneath the MZ in the developing neocortex.

Original languageEnglish
Pages (from-to)223-235
Number of pages13
JournalCerebral Cortex
Volume28
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1

Fingerprint

Cerebral Cortex
Neurons
Neocortex
Brain
Integrins
low density lipoprotein receptor-related protein 8

Keywords

  • ApoER2
  • Cerebral cortex
  • Migration
  • Reelin

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

ApoER2 Controls not only neuronal migration in the intermediate zone but also termination of migration in the developing cerebral cortex. / Hirota, Yuki; Kubo, Kenichiro; Fujino, Takahiro; Yamamoto, Tokuo T.; Nakajima, Kazunori.

In: Cerebral Cortex, Vol. 28, No. 1, 01.01.2018, p. 223-235.

Research output: Contribution to journalArticle

@article{814819d7a7224f9c8c109a41c3fb0d74,
title = "ApoER2 Controls not only neuronal migration in the intermediate zone but also termination of migration in the developing cerebral cortex",
abstract = "Neuronal migration contributes to the establishment of mammalian brain. The extracellular protein Reelin sends signals to various downstream molecules by binding to its receptors, the apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor and exerts essential roles in the neuronal migration and formation of the layered neocortex. However, the cellular and molecular functions of Reelin signaling in the cortical development are not yet fully understood. Here, to gain insight into the role of Reelin signaling during cortical development, we examined the migratory behavior of Apoer2-deficient neurons in the developing brain. Stage-specific labeling of newborn neurons revealed that the neurons ectopically invaded the marginal zone (MZ) and that neuronal migration of both early- and late-born neurons was disrupted in the intermediate zone (IZ) in the Apoer2 KO mice. Rescue experiments showed that ApoER2 functions both in cell-autonomous and noncell-autonomous manners, that Rap1, integrin, and Akt are involved in the termination of migration beneath the MZ, and that Akt also controls neuronal migration in the IZ downstream of ApoER2. These data indicate that ApoER2 controls multiple processes in neuronal migration, including the early stage of radial migration and termination of migration beneath the MZ in the developing neocortex.",
keywords = "ApoER2, Cerebral cortex, Migration, Reelin",
author = "Yuki Hirota and Kenichiro Kubo and Takahiro Fujino and Yamamoto, {Tokuo T.} and Kazunori Nakajima",
year = "2018",
month = "1",
day = "1",
doi = "10.1093/cercor/bhw369",
language = "English",
volume = "28",
pages = "223--235",
journal = "Cerebral Cortex",
issn = "1047-3211",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - ApoER2 Controls not only neuronal migration in the intermediate zone but also termination of migration in the developing cerebral cortex

AU - Hirota, Yuki

AU - Kubo, Kenichiro

AU - Fujino, Takahiro

AU - Yamamoto, Tokuo T.

AU - Nakajima, Kazunori

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Neuronal migration contributes to the establishment of mammalian brain. The extracellular protein Reelin sends signals to various downstream molecules by binding to its receptors, the apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor and exerts essential roles in the neuronal migration and formation of the layered neocortex. However, the cellular and molecular functions of Reelin signaling in the cortical development are not yet fully understood. Here, to gain insight into the role of Reelin signaling during cortical development, we examined the migratory behavior of Apoer2-deficient neurons in the developing brain. Stage-specific labeling of newborn neurons revealed that the neurons ectopically invaded the marginal zone (MZ) and that neuronal migration of both early- and late-born neurons was disrupted in the intermediate zone (IZ) in the Apoer2 KO mice. Rescue experiments showed that ApoER2 functions both in cell-autonomous and noncell-autonomous manners, that Rap1, integrin, and Akt are involved in the termination of migration beneath the MZ, and that Akt also controls neuronal migration in the IZ downstream of ApoER2. These data indicate that ApoER2 controls multiple processes in neuronal migration, including the early stage of radial migration and termination of migration beneath the MZ in the developing neocortex.

AB - Neuronal migration contributes to the establishment of mammalian brain. The extracellular protein Reelin sends signals to various downstream molecules by binding to its receptors, the apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor and exerts essential roles in the neuronal migration and formation of the layered neocortex. However, the cellular and molecular functions of Reelin signaling in the cortical development are not yet fully understood. Here, to gain insight into the role of Reelin signaling during cortical development, we examined the migratory behavior of Apoer2-deficient neurons in the developing brain. Stage-specific labeling of newborn neurons revealed that the neurons ectopically invaded the marginal zone (MZ) and that neuronal migration of both early- and late-born neurons was disrupted in the intermediate zone (IZ) in the Apoer2 KO mice. Rescue experiments showed that ApoER2 functions both in cell-autonomous and noncell-autonomous manners, that Rap1, integrin, and Akt are involved in the termination of migration beneath the MZ, and that Akt also controls neuronal migration in the IZ downstream of ApoER2. These data indicate that ApoER2 controls multiple processes in neuronal migration, including the early stage of radial migration and termination of migration beneath the MZ in the developing neocortex.

KW - ApoER2

KW - Cerebral cortex

KW - Migration

KW - Reelin

UR - http://www.scopus.com/inward/record.url?scp=85017030198&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85017030198&partnerID=8YFLogxK

U2 - 10.1093/cercor/bhw369

DO - 10.1093/cercor/bhw369

M3 - Article

VL - 28

SP - 223

EP - 235

JO - Cerebral Cortex

JF - Cerebral Cortex

SN - 1047-3211

IS - 1

ER -