Ectopic reelin induces neuronal aggregation with a normal birthdate-dependent "inside-out" alignment in the developing neocortex

Kenichiro Kubo, Takao Honda, Kenji Tomita, Katsutoshi Sekine, Kazuhiro Ishii, Asuka Uto, Kazuma Kobayashi, Hidenori Tabata, Kazunori Nakajima

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Neurons in the developing mammalian neocortex form the cortical plate (CP) in an "inside-out" manner; that is, earlier-born neurons form the deeper layers, whereas later-born neurons migrate past the existing layers and form the more superficial layers. Reelin, a glycoprotein secreted by Cajal-Retzius neurons in the marginal zone (MZ), is crucial for this "inside-out" layering, because the layers are inverted in the Reelin-deficient mouse, reeler (Relnrl). Even though more than a decade has passed since the discovery of reelin, the biological effect of Reelin on individual migrating neurons remains unclear. In addition, although the MZ is missing in the reeler cortex, it is unknown whether Reelin directly regulates the development of the cell-body-sparse MZ. To address these issues, we expressed Reelin ectopically in the developing mouse cortex, and the results showed that Reelin caused the leading processes of migrating neurons to assemble in the Reelin-rich region, which in turn induced their cell bodies to form cellular aggregates around Reelin. Interestingly, the ectopic Reelin-rich region became cell-body-sparse and dendrite-rich, resembling the MZ, and the late-born neurons migrated past their predecessors toward the central Reelin-rich region within the aggregates, resulting in a birthdate-dependent "inside-out" alignment even ectopically. Reelin receptors and intracellular adaptor protein Dab1 were found to be necessary for formation of the aggregates. The above findings indicate that Reelin signaling is capable of inducing the formation of the dendrite-rich, cell-body-sparse MZ and a birthdate-dependent "inside-out" alignment of neurons independently of other factors/structures near the MZ.

Original languageEnglish
Pages (from-to)10953-10966
Number of pages14
JournalJournal of Neuroscience
Volume30
Issue number33
DOIs
Publication statusPublished - 2010 Aug 18

Fingerprint

Neocortex
Neurons
Dendrites
Neurologic Mutant Mice
Cerebral Cortex
Glycoproteins
Cell Body

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ectopic reelin induces neuronal aggregation with a normal birthdate-dependent "inside-out" alignment in the developing neocortex. / Kubo, Kenichiro; Honda, Takao; Tomita, Kenji; Sekine, Katsutoshi; Ishii, Kazuhiro; Uto, Asuka; Kobayashi, Kazuma; Tabata, Hidenori; Nakajima, Kazunori.

In: Journal of Neuroscience, Vol. 30, No. 33, 18.08.2010, p. 10953-10966.

Research output: Contribution to journalArticle

Kubo, Kenichiro ; Honda, Takao ; Tomita, Kenji ; Sekine, Katsutoshi ; Ishii, Kazuhiro ; Uto, Asuka ; Kobayashi, Kazuma ; Tabata, Hidenori ; Nakajima, Kazunori. / Ectopic reelin induces neuronal aggregation with a normal birthdate-dependent "inside-out" alignment in the developing neocortex. In: Journal of Neuroscience. 2010 ; Vol. 30, No. 33. pp. 10953-10966.
@article{b901a9af36314012af16b8f2a5b20340,
title = "Ectopic reelin induces neuronal aggregation with a normal birthdate-dependent {"}inside-out{"} alignment in the developing neocortex",
abstract = "Neurons in the developing mammalian neocortex form the cortical plate (CP) in an {"}inside-out{"} manner; that is, earlier-born neurons form the deeper layers, whereas later-born neurons migrate past the existing layers and form the more superficial layers. Reelin, a glycoprotein secreted by Cajal-Retzius neurons in the marginal zone (MZ), is crucial for this {"}inside-out{"} layering, because the layers are inverted in the Reelin-deficient mouse, reeler (Relnrl). Even though more than a decade has passed since the discovery of reelin, the biological effect of Reelin on individual migrating neurons remains unclear. In addition, although the MZ is missing in the reeler cortex, it is unknown whether Reelin directly regulates the development of the cell-body-sparse MZ. To address these issues, we expressed Reelin ectopically in the developing mouse cortex, and the results showed that Reelin caused the leading processes of migrating neurons to assemble in the Reelin-rich region, which in turn induced their cell bodies to form cellular aggregates around Reelin. Interestingly, the ectopic Reelin-rich region became cell-body-sparse and dendrite-rich, resembling the MZ, and the late-born neurons migrated past their predecessors toward the central Reelin-rich region within the aggregates, resulting in a birthdate-dependent {"}inside-out{"} alignment even ectopically. Reelin receptors and intracellular adaptor protein Dab1 were found to be necessary for formation of the aggregates. The above findings indicate that Reelin signaling is capable of inducing the formation of the dendrite-rich, cell-body-sparse MZ and a birthdate-dependent {"}inside-out{"} alignment of neurons independently of other factors/structures near the MZ.",
author = "Kenichiro Kubo and Takao Honda and Kenji Tomita and Katsutoshi Sekine and Kazuhiro Ishii and Asuka Uto and Kazuma Kobayashi and Hidenori Tabata and Kazunori Nakajima",
year = "2010",
month = "8",
day = "18",
doi = "10.1523/JNEUROSCI.0486-10.2010",
language = "English",
volume = "30",
pages = "10953--10966",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "33",

}

TY - JOUR

T1 - Ectopic reelin induces neuronal aggregation with a normal birthdate-dependent "inside-out" alignment in the developing neocortex

AU - Kubo, Kenichiro

AU - Honda, Takao

AU - Tomita, Kenji

AU - Sekine, Katsutoshi

AU - Ishii, Kazuhiro

AU - Uto, Asuka

AU - Kobayashi, Kazuma

AU - Tabata, Hidenori

AU - Nakajima, Kazunori

PY - 2010/8/18

Y1 - 2010/8/18

N2 - Neurons in the developing mammalian neocortex form the cortical plate (CP) in an "inside-out" manner; that is, earlier-born neurons form the deeper layers, whereas later-born neurons migrate past the existing layers and form the more superficial layers. Reelin, a glycoprotein secreted by Cajal-Retzius neurons in the marginal zone (MZ), is crucial for this "inside-out" layering, because the layers are inverted in the Reelin-deficient mouse, reeler (Relnrl). Even though more than a decade has passed since the discovery of reelin, the biological effect of Reelin on individual migrating neurons remains unclear. In addition, although the MZ is missing in the reeler cortex, it is unknown whether Reelin directly regulates the development of the cell-body-sparse MZ. To address these issues, we expressed Reelin ectopically in the developing mouse cortex, and the results showed that Reelin caused the leading processes of migrating neurons to assemble in the Reelin-rich region, which in turn induced their cell bodies to form cellular aggregates around Reelin. Interestingly, the ectopic Reelin-rich region became cell-body-sparse and dendrite-rich, resembling the MZ, and the late-born neurons migrated past their predecessors toward the central Reelin-rich region within the aggregates, resulting in a birthdate-dependent "inside-out" alignment even ectopically. Reelin receptors and intracellular adaptor protein Dab1 were found to be necessary for formation of the aggregates. The above findings indicate that Reelin signaling is capable of inducing the formation of the dendrite-rich, cell-body-sparse MZ and a birthdate-dependent "inside-out" alignment of neurons independently of other factors/structures near the MZ.

AB - Neurons in the developing mammalian neocortex form the cortical plate (CP) in an "inside-out" manner; that is, earlier-born neurons form the deeper layers, whereas later-born neurons migrate past the existing layers and form the more superficial layers. Reelin, a glycoprotein secreted by Cajal-Retzius neurons in the marginal zone (MZ), is crucial for this "inside-out" layering, because the layers are inverted in the Reelin-deficient mouse, reeler (Relnrl). Even though more than a decade has passed since the discovery of reelin, the biological effect of Reelin on individual migrating neurons remains unclear. In addition, although the MZ is missing in the reeler cortex, it is unknown whether Reelin directly regulates the development of the cell-body-sparse MZ. To address these issues, we expressed Reelin ectopically in the developing mouse cortex, and the results showed that Reelin caused the leading processes of migrating neurons to assemble in the Reelin-rich region, which in turn induced their cell bodies to form cellular aggregates around Reelin. Interestingly, the ectopic Reelin-rich region became cell-body-sparse and dendrite-rich, resembling the MZ, and the late-born neurons migrated past their predecessors toward the central Reelin-rich region within the aggregates, resulting in a birthdate-dependent "inside-out" alignment even ectopically. Reelin receptors and intracellular adaptor protein Dab1 were found to be necessary for formation of the aggregates. The above findings indicate that Reelin signaling is capable of inducing the formation of the dendrite-rich, cell-body-sparse MZ and a birthdate-dependent "inside-out" alignment of neurons independently of other factors/structures near the MZ.

UR - http://www.scopus.com/inward/record.url?scp=77955908851&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955908851&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.0486-10.2010

DO - 10.1523/JNEUROSCI.0486-10.2010

M3 - Article

C2 - 20720102

AN - SCOPUS:77955908851

VL - 30

SP - 10953

EP - 10966

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 33

ER -