Epidermal growth factor signaling mediated by Grb2 associated binder1 is required for the spatiotemporally regulated proliferation of Olig2-expressing progenitors in the embryonic spinal cord

Yoshika Hayakawa-Yano, Keigo Nishida, Shinichi Fukami, Yukiko Gotoh, Toshio Hirano, Toshiyuki Nakagawa, Takuya Shimazaki, Hideyuki Okano

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Gab1 (Grb2 associated binder1) has been identified as an adaptor molecule downstream of many growth factors, including epidermal growth factor (EGF), fibroblast growth factor, and platelet-derived growth factor, which have been shown to play crucial roles as mitotic signals for a variety of neural progenitor cells, including stem cells, both in vitro and in vivo. Here, we show that Gab1 deficiency results in a reduction in the number of Olig2-positive (Olig2+) progenitor cells in the developing mouse spinal cord after embryonic day 12.5 (E12.5), when gliogenesis starts in the pMN domain where the EGF receptor (EGFR) is expressed predominantly. Our in vitro analysis further revealed that Gab1 is essential for EGF-dependent proliferation of Olig2 + progenitor cells derived from the E12.5 ventral and E14.5 dorsal but not ventral spinal cord, whereas Gab1 is always required for the activation of Akt1 but not of ERK1/2. Moreover, we found that the action of the Gab1/Akt pathway is context-dependent, since constitutively active Akt1 could rescue the proliferation defect only in the E12.5 spinal cord of the Gab1-deficient mouse in vitro. Finally, we demonstrated that EGFR-deficient mice and Gab1-deficient mice showed a similar reduction in the number of Olig2+ progenitor cells in the developing spinal cord. These findings indicate that EGFR-mediated signaling through Gab1/Akt contributes to the sufficient expansion of Olig2 + progenitor cells in a spatiotemporally regulated manner, which represents the origin of glial cells in the developing spinal cord.

Original languageEnglish
Pages (from-to)1410-1422
Number of pages13
JournalStem Cells
Volume25
Issue number6
DOIs
Publication statusPublished - 2007 Jun

Fingerprint

Epidermal Growth Factor
Spinal Cord
Stem Cells
Epidermal Growth Factor Receptor
Fibroblast Growth Factors
Platelet-Derived Growth Factor
Neuroglia
Intercellular Signaling Peptides and Proteins
In Vitro Techniques

Keywords

  • Epidermal growth factor
  • Grb2 associated binder1
  • Olig2
  • Proliferation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Epidermal growth factor signaling mediated by Grb2 associated binder1 is required for the spatiotemporally regulated proliferation of Olig2-expressing progenitors in the embryonic spinal cord. / Hayakawa-Yano, Yoshika; Nishida, Keigo; Fukami, Shinichi; Gotoh, Yukiko; Hirano, Toshio; Nakagawa, Toshiyuki; Shimazaki, Takuya; Okano, Hideyuki.

In: Stem Cells, Vol. 25, No. 6, 06.2007, p. 1410-1422.

Research output: Contribution to journalArticle

Hayakawa-Yano, Yoshika ; Nishida, Keigo ; Fukami, Shinichi ; Gotoh, Yukiko ; Hirano, Toshio ; Nakagawa, Toshiyuki ; Shimazaki, Takuya ; Okano, Hideyuki. / Epidermal growth factor signaling mediated by Grb2 associated binder1 is required for the spatiotemporally regulated proliferation of Olig2-expressing progenitors in the embryonic spinal cord. In: Stem Cells. 2007 ; Vol. 25, No. 6. pp. 1410-1422.
@article{be670077f3534e5bb695127c9db48702,
title = "Epidermal growth factor signaling mediated by Grb2 associated binder1 is required for the spatiotemporally regulated proliferation of Olig2-expressing progenitors in the embryonic spinal cord",
abstract = "Gab1 (Grb2 associated binder1) has been identified as an adaptor molecule downstream of many growth factors, including epidermal growth factor (EGF), fibroblast growth factor, and platelet-derived growth factor, which have been shown to play crucial roles as mitotic signals for a variety of neural progenitor cells, including stem cells, both in vitro and in vivo. Here, we show that Gab1 deficiency results in a reduction in the number of Olig2-positive (Olig2+) progenitor cells in the developing mouse spinal cord after embryonic day 12.5 (E12.5), when gliogenesis starts in the pMN domain where the EGF receptor (EGFR) is expressed predominantly. Our in vitro analysis further revealed that Gab1 is essential for EGF-dependent proliferation of Olig2 + progenitor cells derived from the E12.5 ventral and E14.5 dorsal but not ventral spinal cord, whereas Gab1 is always required for the activation of Akt1 but not of ERK1/2. Moreover, we found that the action of the Gab1/Akt pathway is context-dependent, since constitutively active Akt1 could rescue the proliferation defect only in the E12.5 spinal cord of the Gab1-deficient mouse in vitro. Finally, we demonstrated that EGFR-deficient mice and Gab1-deficient mice showed a similar reduction in the number of Olig2+ progenitor cells in the developing spinal cord. These findings indicate that EGFR-mediated signaling through Gab1/Akt contributes to the sufficient expansion of Olig2 + progenitor cells in a spatiotemporally regulated manner, which represents the origin of glial cells in the developing spinal cord.",
keywords = "Epidermal growth factor, Grb2 associated binder1, Olig2, Proliferation",
author = "Yoshika Hayakawa-Yano and Keigo Nishida and Shinichi Fukami and Yukiko Gotoh and Toshio Hirano and Toshiyuki Nakagawa and Takuya Shimazaki and Hideyuki Okano",
year = "2007",
month = "6",
doi = "10.1634/stemcells.2006-0584",
language = "English",
volume = "25",
pages = "1410--1422",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Epidermal growth factor signaling mediated by Grb2 associated binder1 is required for the spatiotemporally regulated proliferation of Olig2-expressing progenitors in the embryonic spinal cord

AU - Hayakawa-Yano, Yoshika

AU - Nishida, Keigo

AU - Fukami, Shinichi

AU - Gotoh, Yukiko

AU - Hirano, Toshio

AU - Nakagawa, Toshiyuki

AU - Shimazaki, Takuya

AU - Okano, Hideyuki

PY - 2007/6

Y1 - 2007/6

N2 - Gab1 (Grb2 associated binder1) has been identified as an adaptor molecule downstream of many growth factors, including epidermal growth factor (EGF), fibroblast growth factor, and platelet-derived growth factor, which have been shown to play crucial roles as mitotic signals for a variety of neural progenitor cells, including stem cells, both in vitro and in vivo. Here, we show that Gab1 deficiency results in a reduction in the number of Olig2-positive (Olig2+) progenitor cells in the developing mouse spinal cord after embryonic day 12.5 (E12.5), when gliogenesis starts in the pMN domain where the EGF receptor (EGFR) is expressed predominantly. Our in vitro analysis further revealed that Gab1 is essential for EGF-dependent proliferation of Olig2 + progenitor cells derived from the E12.5 ventral and E14.5 dorsal but not ventral spinal cord, whereas Gab1 is always required for the activation of Akt1 but not of ERK1/2. Moreover, we found that the action of the Gab1/Akt pathway is context-dependent, since constitutively active Akt1 could rescue the proliferation defect only in the E12.5 spinal cord of the Gab1-deficient mouse in vitro. Finally, we demonstrated that EGFR-deficient mice and Gab1-deficient mice showed a similar reduction in the number of Olig2+ progenitor cells in the developing spinal cord. These findings indicate that EGFR-mediated signaling through Gab1/Akt contributes to the sufficient expansion of Olig2 + progenitor cells in a spatiotemporally regulated manner, which represents the origin of glial cells in the developing spinal cord.

AB - Gab1 (Grb2 associated binder1) has been identified as an adaptor molecule downstream of many growth factors, including epidermal growth factor (EGF), fibroblast growth factor, and platelet-derived growth factor, which have been shown to play crucial roles as mitotic signals for a variety of neural progenitor cells, including stem cells, both in vitro and in vivo. Here, we show that Gab1 deficiency results in a reduction in the number of Olig2-positive (Olig2+) progenitor cells in the developing mouse spinal cord after embryonic day 12.5 (E12.5), when gliogenesis starts in the pMN domain where the EGF receptor (EGFR) is expressed predominantly. Our in vitro analysis further revealed that Gab1 is essential for EGF-dependent proliferation of Olig2 + progenitor cells derived from the E12.5 ventral and E14.5 dorsal but not ventral spinal cord, whereas Gab1 is always required for the activation of Akt1 but not of ERK1/2. Moreover, we found that the action of the Gab1/Akt pathway is context-dependent, since constitutively active Akt1 could rescue the proliferation defect only in the E12.5 spinal cord of the Gab1-deficient mouse in vitro. Finally, we demonstrated that EGFR-deficient mice and Gab1-deficient mice showed a similar reduction in the number of Olig2+ progenitor cells in the developing spinal cord. These findings indicate that EGFR-mediated signaling through Gab1/Akt contributes to the sufficient expansion of Olig2 + progenitor cells in a spatiotemporally regulated manner, which represents the origin of glial cells in the developing spinal cord.

KW - Epidermal growth factor

KW - Grb2 associated binder1

KW - Olig2

KW - Proliferation

UR - http://www.scopus.com/inward/record.url?scp=34547114468&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547114468&partnerID=8YFLogxK

U2 - 10.1634/stemcells.2006-0584

DO - 10.1634/stemcells.2006-0584

M3 - Article

VL - 25

SP - 1410

EP - 1422

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

IS - 6

ER -