Fgf signalling through MAPK cascade is required for development of the subpallial telencephalon in zebrafish embryos

Minori Shinya, S. Koshida, A. Sawada, A. Kuroiwa, H. Takeda

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

The telencephalon is formed in the most anterior part of the central nervous system (CNS) and is organised into ventral subpallial and dorsal pallial domains. In mice, it has been demonstrated that Fgf signalling has an important role in induction and patterning of the telencephalon. However, the precise role of Fgf signalling is still unclear, owing to overlapping functions of Fgf family genes. To address this, we have examined, in zebrafish embryos, the activation of Ras/mitogen-activated protein kinase (MAPK), one of the major downstream targets of Fgf signalling. Immunohistochemical analysis reveals that an extracellular signal-regulated kinase (ERK), a vertebrate MAPK is activated in the anterior neural boundary (ANB) of the developing CNS at early segmentation stages. Experiments with Fgf inhibitors reveal that ERK activation at this stage is totally dependent on Fgf signalling. Interestingly, a substantial amount of ERK activation is observed in ace mutants in which fgf8 gene is mutated. We then examine the function of Fgf signalling in telencephalic development by use of several inhibitors to Fgf signalling cascade, including dominant-negative forms of Ras (RasN17) and the Fgf receptor (Fgfr), and a chemical inhibitor of Fgfr, SU5402. In treated embryos, the induction of telencephalic territory normally proceeded but the development of the subpallial telencephalon was suppressed, indicating that Fgf signalling is required for the regionalisation within the telencephalon. Finally, antisense experiments with morpholino-modified oligonucleotides suggest that zebrafish fgf3, which is also expressed in the ANB, cooperates with fgf8 in subpallial development.

Original languageEnglish
Pages (from-to)4153-4164
Number of pages12
JournalDevelopment
Volume128
Issue number21
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Telencephalon
Zebrafish
Mitogen-Activated Protein Kinases
Embryonic Structures
Extracellular Signal-Regulated MAP Kinases
Central Nervous System
Morpholinos
Genes
Vertebrates

Keywords

  • ERK
  • fgf3
  • Morpholino
  • Ras
  • Regionalisation
  • SU5402
  • Zebrafish

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Fgf signalling through MAPK cascade is required for development of the subpallial telencephalon in zebrafish embryos. / Shinya, Minori; Koshida, S.; Sawada, A.; Kuroiwa, A.; Takeda, H.

In: Development, Vol. 128, No. 21, 2001, p. 4153-4164.

Research output: Contribution to journalArticle

Shinya, M, Koshida, S, Sawada, A, Kuroiwa, A & Takeda, H 2001, 'Fgf signalling through MAPK cascade is required for development of the subpallial telencephalon in zebrafish embryos', Development, vol. 128, no. 21, pp. 4153-4164.
Shinya, Minori ; Koshida, S. ; Sawada, A. ; Kuroiwa, A. ; Takeda, H. / Fgf signalling through MAPK cascade is required for development of the subpallial telencephalon in zebrafish embryos. In: Development. 2001 ; Vol. 128, No. 21. pp. 4153-4164.
@article{e689b2ebe3d3405494edfbd2115e6d0f,
title = "Fgf signalling through MAPK cascade is required for development of the subpallial telencephalon in zebrafish embryos",
abstract = "The telencephalon is formed in the most anterior part of the central nervous system (CNS) and is organised into ventral subpallial and dorsal pallial domains. In mice, it has been demonstrated that Fgf signalling has an important role in induction and patterning of the telencephalon. However, the precise role of Fgf signalling is still unclear, owing to overlapping functions of Fgf family genes. To address this, we have examined, in zebrafish embryos, the activation of Ras/mitogen-activated protein kinase (MAPK), one of the major downstream targets of Fgf signalling. Immunohistochemical analysis reveals that an extracellular signal-regulated kinase (ERK), a vertebrate MAPK is activated in the anterior neural boundary (ANB) of the developing CNS at early segmentation stages. Experiments with Fgf inhibitors reveal that ERK activation at this stage is totally dependent on Fgf signalling. Interestingly, a substantial amount of ERK activation is observed in ace mutants in which fgf8 gene is mutated. We then examine the function of Fgf signalling in telencephalic development by use of several inhibitors to Fgf signalling cascade, including dominant-negative forms of Ras (RasN17) and the Fgf receptor (Fgfr), and a chemical inhibitor of Fgfr, SU5402. In treated embryos, the induction of telencephalic territory normally proceeded but the development of the subpallial telencephalon was suppressed, indicating that Fgf signalling is required for the regionalisation within the telencephalon. Finally, antisense experiments with morpholino-modified oligonucleotides suggest that zebrafish fgf3, which is also expressed in the ANB, cooperates with fgf8 in subpallial development.",
keywords = "ERK, fgf3, Morpholino, Ras, Regionalisation, SU5402, Zebrafish",
author = "Minori Shinya and S. Koshida and A. Sawada and A. Kuroiwa and H. Takeda",
year = "2001",
language = "English",
volume = "128",
pages = "4153--4164",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "21",

}

TY - JOUR

T1 - Fgf signalling through MAPK cascade is required for development of the subpallial telencephalon in zebrafish embryos

AU - Shinya, Minori

AU - Koshida, S.

AU - Sawada, A.

AU - Kuroiwa, A.

AU - Takeda, H.

PY - 2001

Y1 - 2001

N2 - The telencephalon is formed in the most anterior part of the central nervous system (CNS) and is organised into ventral subpallial and dorsal pallial domains. In mice, it has been demonstrated that Fgf signalling has an important role in induction and patterning of the telencephalon. However, the precise role of Fgf signalling is still unclear, owing to overlapping functions of Fgf family genes. To address this, we have examined, in zebrafish embryos, the activation of Ras/mitogen-activated protein kinase (MAPK), one of the major downstream targets of Fgf signalling. Immunohistochemical analysis reveals that an extracellular signal-regulated kinase (ERK), a vertebrate MAPK is activated in the anterior neural boundary (ANB) of the developing CNS at early segmentation stages. Experiments with Fgf inhibitors reveal that ERK activation at this stage is totally dependent on Fgf signalling. Interestingly, a substantial amount of ERK activation is observed in ace mutants in which fgf8 gene is mutated. We then examine the function of Fgf signalling in telencephalic development by use of several inhibitors to Fgf signalling cascade, including dominant-negative forms of Ras (RasN17) and the Fgf receptor (Fgfr), and a chemical inhibitor of Fgfr, SU5402. In treated embryos, the induction of telencephalic territory normally proceeded but the development of the subpallial telencephalon was suppressed, indicating that Fgf signalling is required for the regionalisation within the telencephalon. Finally, antisense experiments with morpholino-modified oligonucleotides suggest that zebrafish fgf3, which is also expressed in the ANB, cooperates with fgf8 in subpallial development.

AB - The telencephalon is formed in the most anterior part of the central nervous system (CNS) and is organised into ventral subpallial and dorsal pallial domains. In mice, it has been demonstrated that Fgf signalling has an important role in induction and patterning of the telencephalon. However, the precise role of Fgf signalling is still unclear, owing to overlapping functions of Fgf family genes. To address this, we have examined, in zebrafish embryos, the activation of Ras/mitogen-activated protein kinase (MAPK), one of the major downstream targets of Fgf signalling. Immunohistochemical analysis reveals that an extracellular signal-regulated kinase (ERK), a vertebrate MAPK is activated in the anterior neural boundary (ANB) of the developing CNS at early segmentation stages. Experiments with Fgf inhibitors reveal that ERK activation at this stage is totally dependent on Fgf signalling. Interestingly, a substantial amount of ERK activation is observed in ace mutants in which fgf8 gene is mutated. We then examine the function of Fgf signalling in telencephalic development by use of several inhibitors to Fgf signalling cascade, including dominant-negative forms of Ras (RasN17) and the Fgf receptor (Fgfr), and a chemical inhibitor of Fgfr, SU5402. In treated embryos, the induction of telencephalic territory normally proceeded but the development of the subpallial telencephalon was suppressed, indicating that Fgf signalling is required for the regionalisation within the telencephalon. Finally, antisense experiments with morpholino-modified oligonucleotides suggest that zebrafish fgf3, which is also expressed in the ANB, cooperates with fgf8 in subpallial development.

KW - ERK

KW - fgf3

KW - Morpholino

KW - Ras

KW - Regionalisation

KW - SU5402

KW - Zebrafish

UR - http://www.scopus.com/inward/record.url?scp=0035170549&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035170549&partnerID=8YFLogxK

M3 - Article

C2 - 11684653

AN - SCOPUS:0035170549

VL - 128

SP - 4153

EP - 4164

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 21

ER -