Neuroepithelial secondary organizers and cell fate specification in the developing brain

In vertebrates, elaborate cellular interactions regulate the establishment of the complex structural pattern of the developing central nervous system. Distinct neural and glial identities are acquired by neuroepithelial cells, through progressive restriction of histogenetic potential under the influence of local environmental signals. The localization of the sources of such morphogenetic signals in discrete domains of the developing neural primordium has led to the concept of secondary organizers which refine the identity and polarity of neighboring neuroepithelial regions. Thus, these organizers, secondary to those that operate throughout the embryo during gastrulation, act to pattern the anterior neural plate and tube giving rise to the forebrain, midbrain and hindbrain vesicles. Important progress has recently been made in understanding their genesis and function.

[1]  M. Gulisano,et al.  Nested expression domains of four homeobox genes in developing rostral brain , 1992, Nature.

[2]  R. Beddington,et al.  Anterior patterning in mouse. , 1998, Trends in genetics : TIG.

[3]  I. Cobos,et al.  The avian telencephalic subpallium originates inhibitory neurons that invade tangentially the pallium (dorsal ventricular ridge and cortical areas). , 2001, Developmental biology.

[4]  M. Wassef,et al.  Ectopic induction and reorganization of Wnt-1 expression in quail/chick chimeras. , 1994, Development.

[5]  S. Vaage The segmentation of the primitive neural tube in chick embryos (Gallus domesticus). A morphological, histochemical and autoradiographical investigation. , 1969, Ergebnisse der Anatomie und Entwicklungsgeschichte.

[6]  H. Weiner,et al.  The Sonic Hedgehog-Gli pathway regulates dorsal brain growth and tumorigenesis. , 2001, Development.

[7]  S. Aizawa,et al.  Functional equivalency between Otx2 and Otx1 in development of the rostral head. , 1999, Development.

[8]  T. Lints,et al.  Cooperation of BMP7 and SHH in the Induction of Forebrain Ventral Midline Cells by Prechordal Mesoderm , 1997, Cell.

[9]  J. Rubenstein,et al.  Longitudinal organization of the anterior neural plate and neural tube. , 1995, Development.

[10]  Francis Vella,et al.  Distinct regulators control the expression of the mid-hindbrain organizer signal FGF8 , 2001, Nature Neuroscience.

[11]  R. Beddington,et al.  Axis Development and Early Asymmetry in Mammals , 1999, Cell.

[12]  John L.R. Rubenstein,et al.  Induction and Dorsoventral Patterning of the Telencephalon , 2000, Neuron.

[13]  G. Fishell,et al.  Dorsoventral patterning is established in the telencephalon of mutants lacking both Gli3 and Hedgehog signaling. , 2002, Development.

[14]  P. Brûlet,et al.  Analysis of Fgf15 expression pattern in the mouse neural tube , 2002, Brain Research Bulletin.

[15]  C. Irving,et al.  Signalling by FGF8 from the isthmus patterns anterior hindbrain and establishes the anterior limit of Hox gene expression. , 2000, Development.

[16]  A. Joyner,et al.  Specification of the anterior hindbrain and establishment of a normal mid/hindbrain organizer is dependent on Gbx2 gene function. , 1997, Development.

[17]  C. Irving,et al.  Regeneration of isthmic tissue is the result of a specific and direct interaction between rhombomere 1 and midbrain. , 1999, Development.

[18]  Salvador Martinez,et al.  Midbrain development induced by FGF8 in the chick embryo , 1996, Nature.

[19]  R. Nusse,et al.  Molecular cloning and chromosomal localization to 17q21 of the human WNT3 gene. , 1993, Genomics.

[20]  C. Stern Initial patterning of the central nervous system: How many organizers? , 2001, Nature Reviews Neuroscience.

[21]  T. Kudoh,et al.  Identification of Sef, a novel modulator of FGF signalling , 2002, Nature Cell Biology.

[22]  B. Hogan,et al.  HNF-3β as a regulator of floor plate development , 1994, Cell.

[23]  R. Krumlauf,et al.  Axis duplication and anterior identity in the mouse embryo. , 1997, Cold Spring Harbor symposia on quantitative biology.

[24]  G. Martin,et al.  The mouse Fgf8 gene encodes a family of polypeptides and is expressed in regions that direct outgrowth and patterning in the developing embryo. , 1995, Development.

[25]  N. Hacohen,et al.  Vertebrate Sprouty genes are induced by FGF signaling and can cause chondrodysplasia when overexpressed. , 1999, Development.

[26]  A. Joyner,et al.  EN and GBX2 play essential roles downstream of FGF8 in patterning the mouse mid/hindbrain region. , 2001, Development.

[27]  A. McMahon,et al.  A direct requirement for Hedgehog signaling for normal specification of all ventral progenitor domains in the presumptive mammalian spinal cord. , 2002, Genes & development.

[28]  Wolfgang Wurst,et al.  Neural plate patterning: Upstream and downstream of the isthmic organizer , 2001, Nature Reviews Neuroscience.

[29]  Stephen W. Wilson,et al.  A small population of anterior cells patterns the forebrain during zebrafish gastrulation , 1998, Nature.

[30]  A. Joyner,et al.  Engrailed, Wnt and Pax genes regulate midbrain--hindbrain development. , 1996, Trends in genetics : TIG.

[31]  N. Daigle,et al.  A targeted mouse Otx2 mutation leads to severe defects in gastrulation and formation of axial mesoderm and to deletion of rostral brain. , 1996, Development.

[32]  K. Losos,et al.  FGF8 can activate Gbx2 and transform regions of the rostral mouse brain into a hindbrain fate. , 1999, Development.

[33]  J. Rubenstein,et al.  Molecular regionalization of the neocortex is disrupted in Fgf8 hypomorphic mutants , 2003, Development.

[34]  J. Rubenstein,et al.  Regionalization of the prosencephalic neural plate. , 1998, Annual review of neuroscience.

[35]  I. Cobos,et al.  FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression. , 1999, Development.

[36]  A. Joyner,et al.  Expression patterns of the homeo box-containing genes En-1 and En-2 and the proto-oncogene int-1 diverge during mouse development. , 1988, Genes & development.

[37]  A. Simeone,et al.  Genetic control of brain morphogenesis through Otx gene dosage requirement. , 1997, Development.

[38]  T. Jessell,et al.  The specification of dorsal cell fates in the vertebrate central nervous system. , 1999, Annual review of neuroscience.

[39]  C. Stern,et al.  Segmental organization of embryonic diencephalon , 1993, Nature.

[40]  I. Mason,et al.  Differential Display of Genes Expressed at the Midbrain – Hindbrain Junction Identifies sprouty2: An FGF8-Inducible Member of a Family of Intracellular FGF Antagonists , 2000, Molecular and Cellular Neuroscience.

[41]  R Nieuwenhuys,et al.  The morphological pattern of the vertebrate brain. , 1999, European journal of morphology.

[42]  A. McMahon,et al.  Pax-2 regulatory sequences that direct transgene expression in the developing neural plate and external granule cell layer of the cerebellum. , 1999, Brain research. Developmental brain research.

[43]  L. Puelles,et al.  Segment‐related, mosaic neurogenetic pattern in the forebrain and mesencephalon of early chick embryos: I. Topography of ache‐positive neuroblasts up to stage HH18 , 1987, The Journal of comparative neurology.

[44]  Maria V. Sanchez-Vives,et al.  Reduced junctional permeability at interrhombomeric boundaries. , 1992, Development.

[45]  E. Lai,et al.  Telencephalon-restricted expression of BF-1, a new member of the HNF-3/fork head gene family, in the developing rat brain , 1992, Neuron.

[46]  H. Nakamura,et al.  Plasticity and rigidity of differentiation of brain vesicles studied in quail-chick chimeras. , 1986, Cell differentiation.

[47]  Luis Puelles,et al.  Brain segmentation and forebrain development in amniotes , 2001, Brain Research Bulletin.

[48]  A. Lumsden,et al.  Boundary Formation and Compartition in the Avian Diencephalon , 2001, The Journal of Neuroscience.

[49]  P. Beachy,et al.  Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function , 1996, Nature.

[50]  K. Eto,et al.  Mouse GLI3 regulates Fgf8 expression and apoptosis in the developing neural tube, face, and limb bud. , 2002, Developmental biology.

[51]  C. Nüsslein-Volhard,et al.  Mutations affecting development of the midline and general body shape during zebrafish embryogenesis. , 1996, Development.

[52]  S. Aizawa,et al.  Otx2 is required to respond to signals from anterior neural ridge for forebrain specification. , 2002, Developmental biology.

[53]  G. Martin,et al.  An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination , 1998, Nature Genetics.

[54]  S. Martinez,et al.  Mammalian neural tube grafting experiments: an in vitro system for mouse experimental embryology. , 2001, The International journal of developmental biology.

[55]  R. Alvarado-Mallart,et al.  Fate and potentialities of the avian mesencephalic/metencephalic neuroepithelium. , 1993, Journal of neurobiology.

[56]  W. Wurst,et al.  Otx dose-dependent integrated control of antero-posterior and dorso-ventral patterning of midbrain , 2003, Nature Neuroscience.

[57]  A. Dierich,et al.  Cell autonomous and non-cell autonomous functions of Otx2 in patterning the rostral brain. , 1999, Development.

[58]  Mario R. Capecchi,et al.  Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development , 1990, Nature.

[59]  J. Rubenstein,et al.  Expression Patterns of Two Murine Homologs ofDrosophila Single-MindedSuggest Possible Roles in Embryonic Patterning and in the Pathogenesis of Down Syndrome , 1996, Molecular and Cellular Neuroscience.

[60]  C. A. Gardner,et al.  The cellular environment controls the expression of engrailed-like protein in the cranial neuroepithelium of quail-chick chimeric embryos. , 1991, Development.

[61]  A. Joyner,et al.  Early mesencephalon/metencephalon patterning and development of the cerebellum. , 1997, Perspectives on developmental neurobiology.

[62]  E. Puelles,et al.  Gbx2 expression in the late embryonic chick dorsal thalamus , 2002, Brain Research Bulletin.

[63]  L. Puelles,et al.  A segmental map of architectonic subdivisions in the diencephalon of the frog Rana perezi: acetylcholinesterase-histochemical observations. , 1996, Brain, behavior and evolution.

[64]  Alexandra L. Joyner,et al.  A role for Gbx2 in repression of Otx2 and positioning the mid/hindbrain organizer , 1999, Nature.

[65]  A. McMahon,et al.  Distribution of Sonic hedgehog peptides in the developing chick and mouse embryo. , 1995, Development.

[66]  N. L. Le Douarin,et al.  The fate map of the cephalic neural primordium at the presomitic to the 3-somite stage in the avian embryo. , 1988, Development.

[67]  A. Simeone,et al.  Fgf8 and Gbx2 induction concomitant with Otx2 repression is correlated with midbrain-hindbrain fate of caudal prosencephalon. , 1999, Development.

[68]  J. Rubenstein,et al.  Inductive interactions direct early regionalization of the mouse forebrain. , 1997, Development.

[69]  R. Behringer,et al.  Sequential roles for Otx2 in visceral endoderm and neuroectoderm for forebrain and midbrain induction and specification. , 1998, Development.

[70]  L. Bally-Cuif,et al.  Determination events in the nervous system of the vertebrate embryo. , 1995, Current opinion in genetics & development.

[71]  W. Harris,et al.  Fate of the anterior neural ridge and the morphogenesis of the Xenopus forebrain. , 1995, Journal of neurobiology.

[72]  A. Schier Genetics of neural development in zebrafish , 1997, Current Opinion in Neurobiology.

[73]  A. Joyner,et al.  Multiple developmental defects in Engrailed-1 mutant mice: an early mid-hindbrain deletion and patterning defects in forelimbs and sternum. , 1994, Development.

[74]  Wolfgang Wurst,et al.  The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum , 2003, Development.

[75]  N. Meyer,et al.  The amino-terminal region of Gli3 antagonizes the Shh response and acts in dorsoventral fate specification in the developing spinal cord. , 2003, Developmental biology.

[76]  A. Simeone,et al.  Regionalisation of anterior neuroectoderm and its competence in responding to forebrain and midbrain inducing activities depend on mutual antagonism between OTX2 and GBX2. , 2001, Development.

[77]  S. Martinez,et al.  Expression of the homeobox Chick-en gene in chick/quail chimeras with inverted mes-metencephalic grafts. , 1990, Developmental biology.

[78]  L. Puelles,et al.  Neurogenetic compartments of the mouse diencephalon and some characteristic gene expression patterns. , 2000, Results and problems in cell differentiation.

[79]  L. Puelles,et al.  Patterning of the embryonic avian midbrain after experimental inversions: a polarizing activity from the isthmus. , 1994, Developmental biology.

[80]  Luis Puelles,et al.  A segmental morphological paradigm for understanding vertebrate forebrains. , 1995, Brain, behavior and evolution.

[81]  S. Sugiyama,et al.  Interaction between Otx2 and Gbx2 defines the organizing center for the optic tectum , 2000, Mechanisms of Development.

[82]  J. Rubenstein,et al.  The embryonic vertebrate forebrain: the prosomeric model. , 1994, Science.

[83]  S. Martinez,et al.  The isthmic organizer and brain regionalization. , 2001, The International journal of developmental biology.

[84]  Andrew P. McMahon,et al.  The world according to bedgebog , 1997 .

[85]  Andrew P. McMahon,et al.  The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain , 1990, Cell.

[86]  P. Brûlet,et al.  Forebrain and midbrain regions are deleted in Otx2-/- mutants due to a defective anterior neuroectoderm specification during gastrulation. , 1995, Development.

[87]  E. Grove,et al.  Neocortex Patterning by the Secreted Signaling Molecule FGF8 , 2001, Science.

[88]  M. Busslinger,et al.  Cooperation of Pax2 and Pax5 in midbrain and cerebellum development. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[89]  A. Garcı́a-Bellido Cell proliferation in the attainment of constant sizes and shapes: the Entelechia model. , 1998, The International journal of developmental biology.

[90]  A. Simeone,et al.  Differential transcriptional control as the major molecular event in generating Otx1-/- and Otx2-/- divergent phenotypes. , 1999, Development.

[91]  J. Rubenstein,et al.  FGF and Shh Signals Control Dopaminergic and Serotonergic Cell Fate in the Anterior Neural Plate , 1998, Cell.

[92]  L. Medina,et al.  Organization of the mouse dorsal thalamus based on topology, calretinin immnunostaining, and gene expression , 2002, Brain Research Bulletin.

[93]  A. Joyner,et al.  Otx2 and Gbx2 are required for refinement and not induction of mid-hindbrain gene expression. , 2001, Development.

[94]  A. Prochiantz,et al.  Homeodomain‐Derived Peptides: In and Out of the Cells , 1999, Annals of the New York Academy of Sciences.

[95]  S. Aizawa,et al.  Mouse Otx2 functions in the formation and patterning of rostral head. , 1995, Genes & development.

[96]  Andrew P McMahon,et al.  A mitogen gradient of dorsal midline Wnts organizes growth in the CNS. , 2002, Development.

[97]  R. Harland,et al.  Neural induction by the secreted polypeptide noggin. , 1993, Science.

[98]  I. Cobos,et al.  Fate map of the avian anterior forebrain at the four-somite stage, based on the analysis of quail-chick chimeras. , 2001, Developmental biology.

[99]  M. Brand,et al.  Fgf8 is mutated in zebrafish acerebellar (ace) mutants and is required for maintenance of midbrain-hindbrain boundary development and somitogenesis. , 1998, Development.

[100]  D. Duboule,et al.  Regional expression of the homeobox gene Nkx-2.2 in the developing mammalian forebrain , 1992, Neuron.

[101]  H. Nakamura,et al.  Inductive signal and tissue responsiveness defining the tectum and the cerebellum. , 2001, Development.

[102]  Viktor Hamburger,et al.  A series of normal stages in the development of the chick embryo , 1992, Journal of morphology.

[103]  L. Puelles,et al.  Location of the rostral end of the longitudinal brain axis: Review of an old topic in the light of marking experiments on the closing rostral neuropore , 1987, Journal of morphology.

[104]  H. Nakamura,et al.  Roles of Pax-2 in initiation of the chick tectal development. , 1999, Brain research. Developmental brain research.

[105]  Harukazu Nakamura,et al.  Role of Lmx1b and Wnt1 in mesencephalon and metencephalon development. , 2002, Development.

[106]  A. McMahon,et al.  Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds. , 1993, Development.

[107]  M. Gulisano,et al.  Two vertebrate homeobox genes related to the Drosophila empty spiracles gene are expressed in the embryonic cerebral cortex. , 1992, The EMBO journal.

[108]  Claudio D. Stern,et al.  Patterning the Embryonic Axis FGF Signaling and How Vertebrate Embryos Measure Time , 2001, Cell.

[109]  S. Martinez,et al.  Neuroepithelial co-expression of Gbx2 and Otx2 precedes Fgf8 expression in the isthmic organizer , 2001, Mechanisms of Development.

[110]  M. Hidalgo-Sánchez,et al.  Temporal sequence of gene expression leading caudal prosencephalon to develop a midbrain/hindbrain phenotype , 2002, Developmental dynamics : an official publication of the American Association of Anatomists.

[111]  L. Puelles,et al.  Retrospective clonal analysis of the cerebellum using genetic laacZ/lacZ mouse mosaics. , 1997, Development.

[112]  M. Kessel,et al.  Patterning of the chick forebrain anlage by the prechordal plate. , 1997, Development.

[113]  J. Rubenstein,et al.  Dosage of Fgf8 determines whether cell survival is positively or negatively regulated in the developing forebrain , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[114]  L. Puelles,et al.  Induction of ectopic engrailed expression and fate change in avian rhombomeres: intersegmental boundaries as barriers , 1995, Mechanisms of Development.

[115]  Y. Ohkubo,et al.  Coordinate expression of Fgf8, Otx2, Bmp4, and Shh in the rostral prosencephalon during development of the telencephalic and optic vesicles , 2001, Neuroscience.

[116]  A. Simeone,et al.  The caudal limit of Otx2 gene expression as a marker of the midbrain/hindbrain boundary: a study using in situ hybridisation and chick/quail homotopic grafts. , 1996, Development.

[117]  Andrew P. McMahon,et al.  Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity , 1993, Cell.

[118]  M. Nakafuku,et al.  Early subdivisions in the neural plate define distinct competence for inductive signals. , 2002, Development.

[119]  Qiling Xu,et al.  Eph receptors and ephrins restrict cell intermingling and communication , 1999, Nature.

[120]  Positive and negative signals from mesoderm regulate the expression of mouse Otx2 in ectoderm explants. , 1994, Development.

[121]  H. Meinhardt Cell determination boundaries as organizing regions for secondary embryonic fields. , 1983, Developmental biology.

[122]  P. Doherty,et al.  Sequential roles for Fgf4, En1 and Fgf8 in specification and regionalisation of the midbrain. , 1999, Development.

[123]  W. Cowan,et al.  The development of the chick optic tectum. II. Autoradiographic studies. , 1971, Brain research.

[124]  R. Lehmann,et al.  From screens to genes: prospects for insertional mutagenesis in zebrafish. , 1996, Genes & development.

[125]  Andrew Lumsden,et al.  Patterning the Vertebrate Neuraxis , 1996, Science.

[126]  T. Lints,et al.  Sonic hedgehog induces the differentiation of ventral forebrain neurons: A common signal for ventral patterning within the neural tube , 1995, Cell.

[127]  A. Joyner,et al.  Abnormal embryonic cerebellar development and patterning of postnatal foliation in two mouse Engrailed-2 mutants. , 1994, Development.

[128]  Wolfgang Wurst,et al.  The caudal limit of Otx2 expression positions the isthmic organizer , 1999, Nature.

[129]  A. Simeone,et al.  Retinoic acid induces stage-specific antero-posterior transformation of rostral central nervous system , 1995, Mechanisms of Development.

[130]  T. Jessell,et al.  Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis , 1995, Cell.

[131]  A. Lumsden,et al.  A new developmental compartment in the forebrain regulated by Lunatic fringe , 2001, Nature Neuroscience.

[132]  A. Joyner,et al.  Changing Requirements for Gbx2 in Development of the Cerebellum and Maintenance of the Mid/Hindbrain Organizer , 2002, Neuron.

[133]  A. Fairén,et al.  Prenatal development of calbindin immunoreactivity in the dorsal thalamus of the rat , 1992, Neuroscience.

[134]  S. Millet,et al.  Further observations on the susceptibility of diencephalic prosomeres to En-2 induction and on the resulting histogenetic capabilities , 1996, Mechanisms of Development.

[135]  A. Simeone,et al.  Visceral endoderm-restricted translation of Otx1 mediates recovery of Otx2 requirements for specification of anterior neural plate and normal gastrulation. , 1998, Development.

[136]  M. Fürthauer,et al.  Sef is a feedback-induced antagonist of Ras/MAPK-mediated FGF signalling , 2002, Nature Cell Biology.

[137]  M. Wassef,et al.  Induction of a mesencephalic phenotype in the 2-day-old chick prosencephalon is preceded by the early expression of the homeobox gene en , 1991, Neuron.