Genomic characterisation of a Fgf-regulated gradient-based neocortical protomap

Stephen N. Samson, Jean M. Hebert, Uruporn Thammongkol, James Smith, Grace Nisbet, M. Azim Surani, Susan K. McConnell, Frederick J. Livesey

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Recent findings support a model for neocortical area formation in which neocortical progenitor cells become patterned by extracellular signals to generate a protomap of progenitor cell areas that in turn generate area-specific neurons. The protomap is thought to be underpinned by spatial differences in progenitor cell identity that are reflected at the transcriptional level. We systematically investigated the nature and composition of the protomap by genomic analyses of spatial and temporal neocortical progenitor cell gene expression. We did not find gene expression evidence for progenitor cell organisation into domains or compartments, instead finding rostrocaudal gradients of gene expression across the entire neocortex. Given the role of Fgf signalling in rostrocaudal neocortical patterning, we carried out an in vivo global analysis of cortical gene expression in Fgfr1 mutant mice, identifying consistent alterations in the expression of candidate protomap elements. One such gene, Mest, was predicted by those studies to be a direct target of Fgf8 signalling and to be involved in setting up, rather than implementing, the progenitor cell protomap. In support of this, we confirmed Mest as a direct transcriptional target of Fgf8-regulated signalling in vitro. Functional studies demonstrated that this gene has a role in establishing patterned gene expression in the developing neocortex, potentially by acting as a negative regulator of the Fgf8-controlled patterning system.

Original languageEnglish (US)
Pages (from-to)3947-3961
Number of pages15
JournalDevelopment
Volume132
Issue number17
DOIs
StatePublished - Sep 2005

Fingerprint

Stem Cells
Gene Expression
Neocortex
Spatio-Temporal Analysis
Genes
Neurons

Keywords

  • Microarrays
  • Mouse
  • Neocortex
  • Patterning
  • Protomap

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Samson, S. N., Hebert, J. M., Thammongkol, U., Smith, J., Nisbet, G., Surani, M. A., ... Livesey, F. J. (2005). Genomic characterisation of a Fgf-regulated gradient-based neocortical protomap. Development, 132(17), 3947-3961. https://doi.org/10.1242/dev.01968

Genomic characterisation of a Fgf-regulated gradient-based neocortical protomap. / Samson, Stephen N.; Hebert, Jean M.; Thammongkol, Uruporn; Smith, James; Nisbet, Grace; Surani, M. Azim; McConnell, Susan K.; Livesey, Frederick J.

In: Development, Vol. 132, No. 17, 09.2005, p. 3947-3961.

Research output: Contribution to journalArticle

Samson, SN, Hebert, JM, Thammongkol, U, Smith, J, Nisbet, G, Surani, MA, McConnell, SK & Livesey, FJ 2005, 'Genomic characterisation of a Fgf-regulated gradient-based neocortical protomap', Development, vol. 132, no. 17, pp. 3947-3961. https://doi.org/10.1242/dev.01968
Samson SN, Hebert JM, Thammongkol U, Smith J, Nisbet G, Surani MA et al. Genomic characterisation of a Fgf-regulated gradient-based neocortical protomap. Development. 2005 Sep;132(17):3947-3961. https://doi.org/10.1242/dev.01968
Samson, Stephen N. ; Hebert, Jean M. ; Thammongkol, Uruporn ; Smith, James ; Nisbet, Grace ; Surani, M. Azim ; McConnell, Susan K. ; Livesey, Frederick J. / Genomic characterisation of a Fgf-regulated gradient-based neocortical protomap. In: Development. 2005 ; Vol. 132, No. 17. pp. 3947-3961.
@article{cd44fbc5f4a446a4a8cf6c10befe865f,
title = "Genomic characterisation of a Fgf-regulated gradient-based neocortical protomap",
abstract = "Recent findings support a model for neocortical area formation in which neocortical progenitor cells become patterned by extracellular signals to generate a protomap of progenitor cell areas that in turn generate area-specific neurons. The protomap is thought to be underpinned by spatial differences in progenitor cell identity that are reflected at the transcriptional level. We systematically investigated the nature and composition of the protomap by genomic analyses of spatial and temporal neocortical progenitor cell gene expression. We did not find gene expression evidence for progenitor cell organisation into domains or compartments, instead finding rostrocaudal gradients of gene expression across the entire neocortex. Given the role of Fgf signalling in rostrocaudal neocortical patterning, we carried out an in vivo global analysis of cortical gene expression in Fgfr1 mutant mice, identifying consistent alterations in the expression of candidate protomap elements. One such gene, Mest, was predicted by those studies to be a direct target of Fgf8 signalling and to be involved in setting up, rather than implementing, the progenitor cell protomap. In support of this, we confirmed Mest as a direct transcriptional target of Fgf8-regulated signalling in vitro. Functional studies demonstrated that this gene has a role in establishing patterned gene expression in the developing neocortex, potentially by acting as a negative regulator of the Fgf8-controlled patterning system.",
keywords = "Microarrays, Mouse, Neocortex, Patterning, Protomap",
author = "Samson, {Stephen N.} and Hebert, {Jean M.} and Uruporn Thammongkol and James Smith and Grace Nisbet and Surani, {M. Azim} and McConnell, {Susan K.} and Livesey, {Frederick J.}",
year = "2005",
month = "9",
doi = "10.1242/dev.01968",
language = "English (US)",
volume = "132",
pages = "3947--3961",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "17",

}

TY - JOUR

T1 - Genomic characterisation of a Fgf-regulated gradient-based neocortical protomap

AU - Samson, Stephen N.

AU - Hebert, Jean M.

AU - Thammongkol, Uruporn

AU - Smith, James

AU - Nisbet, Grace

AU - Surani, M. Azim

AU - McConnell, Susan K.

AU - Livesey, Frederick J.

PY - 2005/9

Y1 - 2005/9

N2 - Recent findings support a model for neocortical area formation in which neocortical progenitor cells become patterned by extracellular signals to generate a protomap of progenitor cell areas that in turn generate area-specific neurons. The protomap is thought to be underpinned by spatial differences in progenitor cell identity that are reflected at the transcriptional level. We systematically investigated the nature and composition of the protomap by genomic analyses of spatial and temporal neocortical progenitor cell gene expression. We did not find gene expression evidence for progenitor cell organisation into domains or compartments, instead finding rostrocaudal gradients of gene expression across the entire neocortex. Given the role of Fgf signalling in rostrocaudal neocortical patterning, we carried out an in vivo global analysis of cortical gene expression in Fgfr1 mutant mice, identifying consistent alterations in the expression of candidate protomap elements. One such gene, Mest, was predicted by those studies to be a direct target of Fgf8 signalling and to be involved in setting up, rather than implementing, the progenitor cell protomap. In support of this, we confirmed Mest as a direct transcriptional target of Fgf8-regulated signalling in vitro. Functional studies demonstrated that this gene has a role in establishing patterned gene expression in the developing neocortex, potentially by acting as a negative regulator of the Fgf8-controlled patterning system.

AB - Recent findings support a model for neocortical area formation in which neocortical progenitor cells become patterned by extracellular signals to generate a protomap of progenitor cell areas that in turn generate area-specific neurons. The protomap is thought to be underpinned by spatial differences in progenitor cell identity that are reflected at the transcriptional level. We systematically investigated the nature and composition of the protomap by genomic analyses of spatial and temporal neocortical progenitor cell gene expression. We did not find gene expression evidence for progenitor cell organisation into domains or compartments, instead finding rostrocaudal gradients of gene expression across the entire neocortex. Given the role of Fgf signalling in rostrocaudal neocortical patterning, we carried out an in vivo global analysis of cortical gene expression in Fgfr1 mutant mice, identifying consistent alterations in the expression of candidate protomap elements. One such gene, Mest, was predicted by those studies to be a direct target of Fgf8 signalling and to be involved in setting up, rather than implementing, the progenitor cell protomap. In support of this, we confirmed Mest as a direct transcriptional target of Fgf8-regulated signalling in vitro. Functional studies demonstrated that this gene has a role in establishing patterned gene expression in the developing neocortex, potentially by acting as a negative regulator of the Fgf8-controlled patterning system.

KW - Microarrays

KW - Mouse

KW - Neocortex

KW - Patterning

KW - Protomap

UR - http://www.scopus.com/inward/record.url?scp=26244433711&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=26244433711&partnerID=8YFLogxK

U2 - 10.1242/dev.01968

DO - 10.1242/dev.01968

M3 - Article

C2 - 16079153

AN - SCOPUS:26244433711

VL - 132

SP - 3947

EP - 3961

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 17

ER -