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PMID: 16014716 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Fibroblast growth factor 8 regulates neocortical guidance of area-specific thalamic innervation.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 25 ·No. 28 ·2005-07-13 ·Pages 6550-60

Shimogori T, Grove EA

Abstract

Thalamic innervation of each neocortical area is vital to cortical function, but the developmental strategies that guide axons to specific areas remain unclear. We took a new approach to determine the contribution of intracortical cues. The cortical patterning molecule fibroblast growth factor 8 (FGF8) was misexpressed in the cortical primordium to rearrange the area map. Thalamic axons faithfully tracked changes in area position and innervated duplicated somatosensory barrel fields induced by an ectopic source of FGF8, indicating that thalamic axons indeed use intracortical positional information. Because cortical layers are generated in temporal order, FGF8 misexpression at different ages could be used to shift regional identity in the subplate and cortical plate either in or out of register. Thalamic axons showed strikingly different responses in the two different conditions, disclosing sources of positional guidance in both subplate and cortical plate. Unexpectedly, axon trajectories indicated that an individual neocortical layer could provide not only laminar but also area-specific guidance. Our findings demonstrate that thalamocortical axons are directed by sequential, positional cues within the cortex and implicate FGF8 as an indirect regulator of thalamocortical innervation.

MeSH Terms
Animals Axons/ultrastructure Electroporation Fibroblast Growth Factor 8/genetics,physiology Genes, Reporter Genetic Vectors/administration & dosage,genetics Injections, Intraventricular Mice Neural Pathways/embryology,growth & development Receptor, Fibroblast Growth Factor, Type 3/genetics,physiology Recombinant Fusion Proteins/physiology Somatosensory Cortex/embryology,growth & development Telencephalon/embryology,growth & development Thalamus/embryology,growth & development Transfection Vibrissae/innervation
Chemicals
Fgf8 protein, mouse Recombinant Fusion Proteins Fibroblast Growth Factor 8 FGFR3 protein, human Receptor, Fibroblast Growth Factor, Type 3
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Shimogori Tomomi
Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, Chicago, Illinois 60637, USA.
Grove Elizabeth A
References (74)
74 references, click to expand
  1. Transplants of fetal frontal cortex grafted into the occipital cortex of newborn rats receive a substantial thalamic input from nuclei normally projecting to the frontal cortex.
    Neuroscience. 1999 Mar;89(2):409-21 PMID: 10077323
  2. Molecular evidence for the early specification of presumptive functional domains in the embryonic primate cerebral cortex.
    J Neurosci. 1999 Jul 15;19(14):5967-79 PMID: 10407035
  3. Disrupted cortical map and absence of cortical barrels in growth-associated protein (GAP)-43 knockout mice.
    Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9397-402 PMID: 10430954
  4. Early neocortical regionalization in the absence of thalamic innervation.
    Science. 1999 Aug 6;285(5429):906-9 PMID: 10436162
  5. Genetic control of cortical regionalization and connectivity.
    Cereb Cortex. 1999 Sep;9(6):524-32 PMID: 10498270
  6. Molecular gradients and compartments in the embryonic primate cerebral cortex.
    Cereb Cortex. 1999 Sep;9(6):586-600 PMID: 10498277
  7. Regional differences in the developing cerebral cortex revealed by ephrin-A5 expression.
    Cereb Cortex. 1999 Sep;9(6):601-10 PMID: 10498278
  8. Graded and areal expression patterns of regulatory genes and cadherins in embryonic neocortex independent of thalamocortical input.
    J Neurosci. 1999 Dec 15;19(24):10877-85 PMID: 10594069
  9. Expression of neurotrophin-3 in the mouse forebrain: insights from a targeted LacZ reporter.
    J Comp Neurol. 2000 Jan 17;416(3):398-415 PMID: 10602097
  10. A local Wnt-3a signal is required for development of the mammalian hippocampus.
    Development. 2000 Feb;127(3):457-67 PMID: 10631167
  11. Expression of serotonin transporter protein in developing rat brain.
    Brain Res Dev Brain Res. 2000 Jan 3;119(1):33-45 PMID: 10648870
  12. A mapping label required for normal scale of body representation in the cortex.
    Nat Neurosci. 2000 Apr;3(4):358-65 PMID: 10725925
  13. Regulation of area identity in the mammalian neocortex by Emx2 and Pax6.
    Science. 2000 Apr 14;288(5464):344-9 PMID: 10764649
  14. Induction of visual orientation modules in auditory cortex.
    Nature. 2000 Apr 20;404(6780):841-7 PMID: 10786784
  15. Early commitment of embryonic neocortical cells to develop area-specific thalamic connections.
    Cereb Cortex. 2000 May;10(5):443-53 PMID: 10847594
  16. Area identity shifts in the early cerebral cortex of Emx2-/- mutant mice.
    Nat Neurosci. 2000 Jul;3(7):679-86 PMID: 10862700
  17. Netrin-1 promotes thalamic axon growth and is required for proper development of the thalamocortical projection.
    J Neurosci. 2000 Aug 1;20(15):5792-801 PMID: 10908620
  18. Malformation of the functional organization of somatosensory cortex in adult ephrin-A5 knock-out mice revealed by in vivo functional imaging.
    J Neurosci. 2000 Aug 1;20(15):5841-7 PMID: 10908626
  19. Applications of microelectroporation for studies of chick embryogenesis.
    Dev Growth Differ. 2000 Jun;42(3):203-6 PMID: 10910125
  20. Cortex-restricted disruption of NMDAR1 impairs neuronal patterns in the barrel cortex.
    Nature. 2000 Aug 17;406(6797):726-31 PMID: 10963597
  21. Efficient in utero gene transfer system to the developing mouse brain using electroporation: visualization of neuronal migration in the developing cortex.
    Neuroscience. 2001;103(4):865-72 PMID: 11301197
  22. Combinatorial expression patterns of LIM-homeodomain and other regulatory genes parcellate developing thalamus.
    J Neurosci. 2001 Apr 15;21(8):2711-25 PMID: 11306624
  23. Attraction exerted in vivo by grafts of embryonic neocortex on developing thalamic axons.
    Exp Neurol. 2001 Jun;169(2):264-75 PMID: 11358441
  24. Neocortex patterning by the secreted signaling molecule FGF8.
    Science. 2001 Nov 2;294(5544):1071-4 PMID: 11567107
  25. Emx2 and Pax6 control regionalization of the pre-neuronogenic cortical primordium.
    Cereb Cortex. 2002 Feb;12(2):129-39 PMID: 11739261
  26. Thalamic relay functions and their role in corticocortical communication: generalizations from the visual system.
    Neuron. 2002 Jan 17;33(2):163-75 PMID: 11804565
  27. Patterning centers, regulatory genes and extrinsic mechanisms controlling arealization of the neocortex.
    Curr Opin Neurobiol. 2002 Feb;12(1):14-25 PMID: 11861160
  28. Cortical and thalamic axon pathfinding defects in Tbr1, Gbx2, and Pax6 mutant mice: evidence that cortical and thalamic axons interact and guide each other.
    J Comp Neurol. 2002 May 20;447(1):8-17 PMID: 11967891
  29. A novel role for p75NTR in subplate growth cone complexity and visual thalamocortical innervation.
    J Neurosci. 2002 May 1;22(9):3580-93 PMID: 11978834
  30. Massive cross-modal cortical plasticity and the emergence of a new cortical area in developmentally blind mammals.
    Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11429-34 PMID: 12163645
  31. Distinct actions of Emx1, Emx2, and Pax6 in regulating the specification of areas in the developing neocortex.
    J Neurosci. 2002 Sep 1;22(17):7627-38 PMID: 12196586
  32. Role of Emx2 in the development of the reciprocal connectivity between cortex and thalamus.
    J Comp Neurol. 2002 Sep 16;451(2):153-69 PMID: 12209834
  33. Ephrin-B3-EphA4 interactions regulate the growth of specific thalamocortical axon populations in vitro.
    Eur J Neurosci. 2002 Sep;16(6):1168-72 PMID: 12383247
  34. Miswiring of limbic thalamocortical projections in the absence of ephrin-A5.
    J Neurosci. 2002 Nov 1;22(21):9352-7 PMID: 12417660
  35. The early topography of thalamocortical projections is shifted in Ebf1 and Dlx1/2 mutant mice.
    Development. 2002 Dec;129(24):5621-34 PMID: 12421703
  36. Neurotrophin-3 is required for appropriate establishment of thalamocortical connections.
    Neuron. 2002 Nov 14;36(4):623-34 PMID: 12441052
  37. Normal development of embryonic thalamocortical connectivity in the absence of evoked synaptic activity.
    J Neurosci. 2002 Dec 1;22(23):10313-23 PMID: 12451131
  38. EphA family gene expression in the developing mouse neocortex: regional patterns reveal intrinsic programs and extrinsic influence.
    J Comp Neurol. 2003 Feb 10;456(3):203-16 PMID: 12528186
  39. Emx1 and Emx2 cooperate to regulate cortical size, lamination, neuronal differentiation, development of cortical efferents, and thalamocortical pathfinding.
    J Comp Neurol. 2003 Mar 17;457(4):345-60 PMID: 12561075
  40. The role of the thalamus in the flow of information to the cortex.
    Philos Trans R Soc Lond B Biol Sci. 2002 Dec 29;357(1428):1695-708 PMID: 12626004
  41. Molecular regionalization of the neocortex is disrupted in Fgf8 hypomorphic mutants.
    Development. 2003 May;130(9):1903-14 PMID: 12642494
  42. Thalamocortical development: how are we going to get there?
    Nat Rev Neurosci. 2003 Apr;4(4):276-89 PMID: 12671644
  43. Emx2 patterns the neocortex by regulating FGF positional signaling.
    Nat Neurosci. 2003 Aug;6(8):825-31 PMID: 12872126
  44. Neurogenin2 specifies the connectivity of thalamic neurons by controlling axon responsiveness to intermediate target cues.
    Neuron. 2003 Jul 31;39(3):439-52 PMID: 12895419
  45. Area specificity and topography of thalamocortical projections are controlled by ephrin/Eph genes.
    Neuron. 2003 Jul 31;39(3):453-65 PMID: 12895420
  46. Generating the cerebral cortical area map.
    Annu Rev Neurosci. 2003;26:355-80 PMID: 14527269
  47. EMX2 regulates sizes and positioning of the primary sensory and motor areas in neocortex by direct specification of cortical progenitors.
    Neuron. 2004 Aug 5;43(3):359-72 PMID: 15294144
  48. Intermediate targets in formation of topographic projections: inputs from the thalamocortical system.
    Trends Neurosci. 2004 Sep;27(9):533-9 PMID: 15331235
  49. Fgf8 regulates the development of intra-neocortical projections.
    J Neurosci. 2004 Oct 13;24(41):8917-23 PMID: 15483110
  50. Attraction of specific thalamic input by cerebral grafts depends on the molecular identity of the implant.
    Proc Natl Acad Sci U S A. 1992 May 1;89(9):3706-10 PMID: 1570290
  51. Cross-modal plasticity in cortical development: differentiation and specification of sensory neocortex.
    Trends Neurosci. 1990 Jun;13(6):227-33 PMID: 1694329
  52. A novel cytoarchitectonic area induced experimentally within the primate visual cortex.
    Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2083-7 PMID: 2006147
  53. Transient patterns of GAP-43 expression during the formation of barrels in the rat somatosensory cortex.
    J Comp Neurol. 1990 Feb 15;292(3):443-56 PMID: 2160480
  54. Thalamic axons confer a blueprint of the sensory periphery onto the developing rat somatosensory cortex.
    Brain Res Dev Brain Res. 1990 Nov 1;56(2):229-34 PMID: 2261684
  55. Functional synaptic circuits in the subplate during fetal and early postnatal development of cat visual cortex.
    J Neurosci. 1990 Aug;10(8):2601-13 PMID: 2388080
  56. Requirement for subplate neurons in the formation of thalamocortical connections.
    Nature. 1990 Sep 13;347(6289):179-81 PMID: 2395469
  57. Developmental history of the transient subplate zone in the visual and somatosensory cortex of the macaque monkey and human brain.
    J Comp Neurol. 1990 Jul 15;297(3):441-70 PMID: 2398142
  58. Experimentally induced visual projections into auditory thalamus and cortex.
    Science. 1988 Dec 9;242(4884):1437-41 PMID: 2462279
  59. Specification of cerebral cortical areas.
    Science. 1988 Jul 8;241(4862):170-6 PMID: 3291116
  60. Studies of the earliest generated cells of the cat's visual cortex: cogeneration of subplate and marginal zones.
    J Neurosci. 1985 Apr;5(4):1062-75 PMID: 3981242
  61. Somatosensory cortex: structural alterations following early injury to sense organs.
    Science. 1973 Jan 26;179(4071):395-8 PMID: 4682966
  62. The structural organization of layer IV in the somatosensory region (SI) of mouse cerebral cortex. The description of a cortical field composed of discrete cytoarchitectonic units.
    Brain Res. 1970 Jan 20;17(2):205-42 PMID: 4904874
  63. Mouse somatosensory cortex: alterations in the barrelfield following receptor injury at different early postnatal ages.
    Neuroscience. 1981;6(8):1503-35 PMID: 7266876
  64. Age-dependent specification of the corticocortical connections of cerebral grafts.
    J Neurosci. 1995 Mar;15(3 Pt 1):1819-34 PMID: 7891137
  65. The subplate, a transient neocortical structure: its role in the development of connections between thalamus and cortex.
    Annu Rev Neurosci. 1994;17:185-218 PMID: 8210173
  66. Specification of neocortical areas and thalamocortical connections.
    Annu Rev Neurosci. 1994;17:419-39 PMID: 8210182
  67. A role for subplate neurons in the patterning of connections from thalamus to neocortex.
    Development. 1993 Mar;117(3):1031-47 PMID: 8325233
  68. Neuronal circuits are subdivided by differential expression of type-II classic cadherins in postnatal mouse brains.
    Mol Cell Neurosci. 1997;9(5-6):433-47 PMID: 9361280
  69. Regulation of thalamic neurite outgrowth by the Eph ligand ephrin-A5: implications in the development of thalamocortical projections.
    Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5329-34 PMID: 9560275
  70. Cadherin-6 in the developing mouse brain: expression along restricted connection systems and synaptic localization suggest a potential role in neuronal circuitry.
    Dev Dyn. 1998 Apr;211(4):338-51 PMID: 9566953
  71. The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in Gli3-deficient mice.
    Development. 1998 Jun;125(12):2315-25 PMID: 9584130
  72. Mechanisms underlying the early establishment of thalamocortical connections in the rat.
    J Neurosci. 1998 Aug 1;18(15):5723-45 PMID: 9671663
  73. The role of the first postmitotic cortical cells in the development of thalamocortical innervation in the reeler mouse.
    J Neurosci. 1998 Aug 1;18(15):5746-65 PMID: 9671664
  74. Generalized lacZ expression with the ROSA26 Cre reporter strain.
    Nat Genet. 1999 Jan;21(1):70-1 PMID: 9916792
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.0453-05.2005
Published
2005-07-13
Pages
6550-60
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6725424
Subset
IM
Grants
NICHD NIH HHS · R01 HD042330 · United States
NICHD NIH HHS · R01HD42330 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.0453-05.2005 PMC Full Text View journal details
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