Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
AAAS Promotion

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Originally published in Science Express on 20 September 2001
Science 2 November 2001:
Vol. 294. no. 5544, pp. 1071 - 1074
DOI: 10.1126/science.1064252

Research Articles

Neocortex Patterning by the Secreted Signaling Molecule FGF8

Tomomi Fukuchi-Shimogori, Elizabeth A. Grove*

A classic model proposes that the mammalian neocortex is divided into areas early in neurogenesis, but the molecular mechanisms that generate the area map have been elusive. Here we provide evidence that FGF8 regulates development of the map from a source in the anterior telencephalon. Using electroporation-mediated gene transfer in mouse embryos, we show that augmenting the endogenous anterior FGF8 signal shifts area boundaries posteriorly, reducing the signal shifts them anteriorly, and introducing a posterior source of FGF8 elicits partial area duplications, revealed by ectopic somatosensory barrel fields. These findings support a role for FGF signaling in specifying positional identity in the neocortex.

Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, IL 60637, USA.
*   To whom correspondence should be addressed. E-mail: egrove{at}drugs.bsd.uchicago.edu


Read the Full Text



THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
In DRG11 Knock-Out Mice, Trigeminal Cell Death Is Extensive and Does Not Account for Failed Brainstem Patterning.
M. F. Jacquin, J. J. A. Arends, C. Xiang, L. A. Shapiro, C. E. Ribak, and Z.-F. Chen (2008)
J. Neurosci. 28, 3577-3585
   Abstract »    Full Text »    PDF »
Possible involvement of SINEs in mammalian-specific brain formation.
T. Sasaki, H. Nishihara, M. Hirakawa, K. Fujimura, M. Tanaka, N. Kokubo, C. Kimura-Yoshida, I. Matsuo, K. Sumiyama, N. Saitou, et al. (2008)
PNAS 105, 4220-4225
   Abstract »    Full Text »    PDF »
Nuclear Receptor TLX Regulates Cell Cycle Progression in Neural Stem Cells of the Developing Brain.
W. Li, G. Sun, S. Yang, Q. Qu, K. Nakashima, and Y. Shi (2008)
Mol. Endocrinol. 22, 56-64
   Abstract »    Full Text »    PDF »
Differential Gene Expression between Sensory Neocortical Areas: Potential Roles for Ten_m3 and Bcl6 in Patterning Visual and Somatosensory Pathways.
C. A. Leamey, K. A. Glendining, G. Kreiman, N.-D. Kang, K. H. Wang, R. Fassler, A. Sawatari, S. Tonegawa, and M. Sur (2008)
Cereb Cortex 18, 53-66
   Abstract »    Full Text »    PDF »
COUP-TFI Coordinates Cortical Patterning, Neurogenesis, and Laminar Fate and Modulates MAPK/ERK, AKT, and {beta}-Catenin Signaling.
A. Faedo, G. S. Tomassy, Y. Ruan, H. Teichmann, S. Krauss, S. J. Pleasure, S. Y. Tsai, M.-J. Tsai, M. Studer, and J. L. R. Rubenstein (2007)
Cereb Cortex
   Abstract »    Full Text »    PDF »
Fgf8 induces pillar cell fate and regulates cellular patterning in the mammalian cochlea.
B. E. Jacques, M. E. Montcouquiol, E. M. Layman, M. Lewandoski, and M. W. Kelley (2007)
Development 134, 3021-3029
   Abstract »    Full Text »    PDF »
Patterning of frontal cortex subdivisions by Fgf17.
J. A. Cholfin and J. L. R. Rubenstein (2007)
PNAS 104, 7652-7657
   Abstract »    Full Text »    PDF »
Development of Cortical Maps: Perspectives From the Barrel Cortex.
M. Inan and M. C. Crair (2007)
Neuroscientist 13, 49-61
   Abstract »    PDF »
Dose-dependent functions of Fgf8 in regulating telencephalic patterning centers.
E. E. Storm, S. Garel, U. Borello, J. M. Hebert, S. Martinez, S. K. McConnell, G. R. Martin, and J. L. R. Rubenstein (2006)
Development 133, 1831-1844
   Abstract »    Full Text »    PDF »
Role of efficient neurotransmitter release in barrel map development..
H.-C. Lu, D. A. Butts, P. S. Kaeser, W.-C. She, R. Janz, and M. C. Crair (2006)
J. Neurosci. 26, 2692-2703
   Abstract »    Full Text »    PDF »
Molecular and Morphological Heterogeneity of Neural Precursors in the Mouse Neocortical Proliferative Zones.
J. S. Gal, Y. M. Morozov, A. E. Ayoub, M. Chatterjee, P. Rakic, and T. F. Haydar (2006)
J. Neurosci. 26, 1045-1056
   Abstract »    Full Text »    PDF »
Role of the Protomap and Target-derived Signals in the Development of Intrahemispheric Connections.
W. Bai, M. Ishida, M. Okabe, and Y. Arimatsu (2006)
Cereb Cortex 16, 124-135
   Abstract »    Full Text »    PDF »
A developmental and genetic classification for malformations of cortical development.
A. J. Barkovich, R. I. Kuzniecky, G. D. Jackson, R. Guerrini, and W. B. Dobyns (2005)
Neurology 65, 1873-1887
   Abstract »    Full Text »    PDF »
A Morphogenetic Model for the Development of Cortical Convolutions.
R. Toro and Y. Burnod (2005)
Cereb Cortex 15, 1900-1913
   Abstract »    Full Text »    PDF »
Fgf8 expression defines a morphogenetic center required for olfactory neurogenesis and nasal cavity development in the mouse.
S. Kawauchi, J. Shou, R. Santos, J. M. Hebert, S. K. McConnell, I. Mason, and A. L. Calof (2005)
Development 132, 5211-5223
   Abstract »    Full Text »    PDF »
Patterning and Plasticity of the Cerebral Cortex.
M. Sur and J. L. R. Rubenstein (2005)
Science 310, 805-810
   Abstract »    Full Text »    PDF »
Map Plasticity in Somatosensory Cortex.
D. E. Feldman and M. Brecht (2005)
Science 310, 810-815
   Abstract »    Full Text »    PDF »
Genomic characterisation of a Fgf-regulated gradient-based neocortical protomap.
S. N. Sansom, J. M. Hebert, U. Thammongkol, J. Smith, G. Nisbet, M. A. Surani, S. K. McConnell, and F. J. Livesey (2005)
Development 132, 3947-3961
   Abstract »    Full Text »    PDF »
Cortical development: the art of generating cell diversity.
M. Gotz and L. Sommer (2005)
Development 132, 3327-3332
   Abstract »    Full Text »    PDF »
Fibroblast Growth Factor 8 Regulates Neocortical Guidance of Area-Specific Thalamic Innervation.
T. Shimogori and E. A. Grove (2005)
J. Neurosci. 25, 6550-6560
   Abstract »    Full Text »    PDF »
Foxg1 Confines Cajal-Retzius Neuronogenesis and Hippocampal Morphogenesis to the Dorsomedial Pallium.
L. Muzio and A. Mallamaci (2005)
J. Neurosci. 25, 4435-4441
   Abstract »    Full Text »    PDF »
Two minds about odors.
L. M. Kay (2004)
PNAS 101, 17569-17570
   Full Text »    PDF »
Embryonic signaling centers expressing BMP, WNT and FGF proteins interact to pattern the cerebral cortex.
T. Shimogori, V. Banuchi, H. Y. Ng, J. B. Strauss, and E. A. Grove (2004)
Development 131, 5639-5647
   Abstract »    Full Text »    PDF »
Fgf8 Regulates the Development of Intra-Neocortical Projections.
K. J. Huffman, S. Garel, and J. L. R. Rubenstein (2004)
J. Neurosci. 24, 8917-8923
   Abstract »    Full Text »    PDF »
bHLH Gene Expression in the Emx2-deficient Dentate Gyrus Reveals Defective Granule Cells and Absence of Migrating Precursors.
J. Oldekamp, N. Kraemer, G. Alvarez-Bolado, and T. Skutella (2004)
Cereb Cortex 14, 1045-1058
   Abstract »    Full Text »    PDF »
Gene Expression Analysis of the Late Embryonic Mouse Cerebral Cortex Using DNA Microarray: Identification of Several Region- and Layer-specific Genes.
N. Funatsu, T. Inoue, and S. Nakamura (2004)
Cereb Cortex 14, 1031-1044
   Abstract »    Full Text »    PDF »
Fibroblast Growth Factor Receptor 1 Is Required for the Proliferation of Hippocampal Progenitor Cells and for Hippocampal Growth in Mouse.
Y. Ohkubo, A. O. Uchida, D. Shin, J. Partanen, and F. M. Vaccarino (2004)
J. Neurosci. 24, 6057-6069
   Abstract »    Full Text »    PDF »
G Protein-Coupled Receptor-Dependent Development of Human Frontal Cortex.
X. Piao, R. S. Hill, A. Bodell, B. S. Chang, L. Basel-Vanagaite, R. Straussberg, W. B. Dobyns, B. Qasrawi, R. M. Winter, A. M. Innes, et al. (2004)
Science 303, 2033-2036
   Abstract »    Full Text »    PDF »
Novel Neuronal Phenotypes from Neural Progenitor Cells.
E. A. Markakis, T. D. Palmer, L. Randolph-Moore, P. Rakic, and F. H. Gage (2004)
J. Neurosci. 24, 2886-2897
   Abstract »    Full Text »    PDF »
Loss of Glutamatergic Pyramidal Neurons in Frontal and Temporal Cortex Resulting from Attenuation of FGFR1 Signaling Is Associated with Spontaneous Hyperactivity in Mice.
D. M. Shin, S. Korada, R. Raballo, C. S. Shashikant, A. Simeone, J. R. Taylor, and F. Vaccarino (2004)
J. Neurosci. 24, 2247-2258
   Abstract »    Full Text »    PDF »
Misrouting of mitral cell progenitors in the Pax6/small eyerat telencephalon.
T. Nomura and N. Osumi (2004)
Development 131, 787-796
   Abstract »    Full Text »    PDF »
Spatial and temporal expression of heparan sulfate in mouse development regulates FGF and FGF receptor assembly.
B. L. Allen and A. C. Rapraeger (2003)
J. Cell Biol. 163, 637-648
   Abstract »    Full Text »    PDF »
Unique and combinatorial functions of Fgf3 and Fgf8 during zebrafish forebrain development.
J. Walshe and I. Mason (2003)
Development 130, 4337-4349
   Abstract »    Full Text »    PDF »
Calmodulin Regulates Synaptic Plasticity in the Anterior Cingulate Cortex and Behavioral Responses: A Microelectroporation Study in Adult Rodents.
F. Wei, X.-M. Xia, J. Tang, H. Ao, S. Ko, J. Liauw, C.-S. Qiu, and M. Zhuo (2003)
J. Neurosci. 23, 8402-8409
   Abstract »    Full Text »    PDF »
Expression of the Transcription Factor, tailless, Is Required for Formation of Superficial Cortical Layers.
P. W. Land and A. P. Monaghan (2003)
Cereb Cortex 13, 921-931
   Abstract »    Full Text »    PDF »
Identification of a Pax6-Dependent Epidermal Growth Factor Family Signaling Source at the Lateral Edge of the Embryonic Cerebral Cortex.
S. Assimacopoulos, E. A. Grove, and C. W. Ragsdale (2003)
J. Neurosci. 23, 6399-6403
   Abstract »    Full Text »    PDF »
Four-Dimensional Migratory Coordinates of GABAergic Interneurons in the Developing Mouse Cortex.
E. S. B. C. Ang Jr, T. F. Haydar, V. Gluncic, and P. Rakic (2003)
J. Neurosci. 23, 5805-5815
   Abstract »    Full Text »    PDF »
Wnt Regulation of Progenitor Maturation in the Cortex Depends on Shh or Fibroblast Growth Factor 2.
J. Viti, A. Gulacsi, and L. Lillien (2003)
J. Neurosci. 23, 5919-5927
   Abstract »    Full Text »    PDF »
Emx1, Emx2 and Pax6 in Specification, Regionalization and Arealization of the Cerebral Cortex.
L. Muzio and A. Mallamaci (2003)
Cereb Cortex 13, 641-647
   Abstract »    Full Text »    PDF »
Choreography of Early Thalamocortical Development.
Z. Molnar, S. Higashi, and G. Lopez-Bendito (2003)
Cereb Cortex 13, 661-669
   Abstract »    Full Text »    PDF »
Molecular regionalization of the neocortex is disrupted in Fgf8 hypomorphic mutants.
S. Garel, K. J. Huffman, and J. L. R. Rubenstein (2003)
Development 130, 1903-1914
   Abstract »    Full Text »    PDF »
Fibroblast growth factors as regulators of central nervous system development and function.
R. Dono (2003)
Am J Physiol Regulatory Integrative Comp Physiol 284, R867-R881
   Abstract »    Full Text »    PDF »
FGF signaling through FGFR1 is required for olfactory bulb morphogenesis.
J. M. Hebert, M. Lin, J. Partanen, J. Rossant, and S. K. McConnell (2003)
Development 130, 1101-1111
   Abstract »    Full Text »    PDF »
Dosage of Fgf8 determines whether cell survival is positively or negatively regulated in the developing forebrain.
E. E. Storm, J. L. R. Rubenstein, and G. R. Martin (2003)
PNAS 100, 1757-1762
   Abstract »    Full Text »    PDF »
Early Differences in Axonal Outgrowth, Cell Migration and GABAergic Differentiation Properties between the Dorsal and Lateral Cortex.
A. Bellion, M. Wassef, and C. Metin (2003)
Cereb Cortex 13, 203-214
   Abstract »    Full Text »    PDF »
Fibroblast Growth Factor Receptor 3 Signaling Regulates the Onset of Oligodendrocyte Terminal Differentiation.
L. Y. S. Oh, A. Denninger, J. S. Colvin, A. Vyas, S. Tole, D. M. Ornitz, and R. Bansal (2003)
J. Neurosci. 23, 883-894
   Abstract »    Full Text »    PDF »
Variant heparan sulfates synthesized in developing mouse brain differentially regulate FGF signaling.
M. Ford-Perriss, S. E. Guimond, U. Greferath, M. Kita, K. Grobe, H. Habuchi, K. Kimata, J. D. Esko, M. Murphy, and J. E. Turnbull (2002)
Glycobiology 12, 721-727
   Abstract »    Full Text »    PDF »
Miswiring of Limbic Thalamocortical Projections in the Absence of Ephrin-A5.
D. Uziel, S. Muhlfriedel, K. Zarbalis, W. Wurst, P. Levitt, and J. Bolz (2002)
J. Neurosci. 22, 9352-9357
   Abstract »    Full Text »    PDF »
The Pyramidal Cell of the Sensorimotor Cortex of the Macaque Monkey: Phenotypic Variation.
G. N. Elston and K. S. Rockland (2002)
Cereb Cortex 12, 1071-1078
   Abstract »    Full Text »    PDF »
Refinement of Thalamocortical Arbors and Emergence of Barrel Domains in the Primary Somatosensory Cortex: A Study of Normal and Monoamine Oxidase A Knock-Out Mice.
A. Rebsam, I. Seif, and P. Gaspar (2002)
J. Neurosci. 22, 8541-8552
   Abstract »    Full Text »    PDF »
Distinct Actions of Emx1, Emx2, and Pax6 in Regulating the Specification of Areas in the Developing Neocortex.
K. M. Bishop, J. L. R. Rubenstein, and D. D. M. O'Leary (2002)
J. Neurosci. 22, 7627-7638
   Abstract »    Full Text »    PDF »
Induction and patterning of the telencephalon in Xenopus laevis.
G. Lupo, W. A. Harris, G. Barsacchi, and R. Vignali (2002)
Development 129, 5421-5436
   Abstract »    Full Text »    PDF »



ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products