Genomic Perspectives of Transcriptional Regulation in Forebrain Development

The forebrain is the seat of higher-order brain functions, and many human neuropsychiatric disorders are due to genetic defects affecting forebrain development, making it imperative to understand the underlying genetic circuitry. Recent progress now makes it possible to begin fully elucidating the genomic regulatory mechanisms that control forebrain gene expression. Herein, we discuss the current knowledge of how transcription factors drive gene expression programs through their interactions with cis-acting genomic elements, such as enhancers; how analyses of chromatin and DNA modifications provide insights into gene expression states; and how these approaches yield insights into the evolution of the human brain.

[1]  Laura E. DeMare,et al.  The genomic landscape of cohesin-associated chromatin interactions , 2013, Genome research.

[2]  R. Gibbs,et al.  PipMaker--a web server for aligning two genomic DNA sequences. , 2000, Genome research.

[3]  M. Sur,et al.  Reduced conditioned fear response in mice that lack Dlx1 and show subtype-specific loss of interneurons , 2009, Journal of Neurodevelopmental Disorders.

[4]  S. Scherer,et al.  Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing. , 2013, American journal of human genetics.

[5]  Colby G Starker,et al.  In vivo Genome Editing Using High Efficiency TALENs , 2012, Nature.

[6]  P. Ellen Grant,et al.  Evolutionarily Dynamic Alternative Splicing of GPR56 Regulates Regional Cerebral Cortical Patterning , 2014, Science.

[7]  T. Bliss,et al.  Loss of forebrain cholinergic neurons and impairment in spatial learning and memory in LHX7‐deficient mice , 2005, The European journal of neuroscience.

[8]  J. Rubenstein,et al.  Null mutation of Dlx-2 results in abnormal morphogenesis of proximal first and second branchial arch derivatives and abnormal differentiation in the forebrain. , 1995, Genes & development.

[9]  J. Winkler,et al.  Heterozygous mutations in SIX3 and SHH are associated with schizencephaly and further expand the clinical spectrum of holoprosencephaly , 2010, Human Genetics.

[10]  David A. Orlando,et al.  Mediator and Cohesin Connect Gene Expression and Chromatin Architecture , 2010, Nature.

[11]  Ivan Ovcharenko,et al.  ECR Browser: a tool for visualizing and accessing data from comparisons of multiple vertebrate genomes , 2004, Nucleic Acids Res..

[12]  G. Miyoshi,et al.  The Requirement of Nkx2-1 in the Temporal Specification of Cortical Interneuron Subtypes , 2008, Neuron.

[13]  Łukasz M. Boryń,et al.  Genome-Wide Quantitative Enhancer Activity Maps Identified by STARR-seq , 2013, Science.

[14]  Shane J. Neph,et al.  Circuitry and Dynamics of Human Transcription Factor Regulatory Networks , 2012, Cell.

[15]  Shyam Prabhakar,et al.  Close sequence comparisons are sufficient to identify human cis-regulatory elements. , 2005, Genome research.

[16]  J. Rubenstein,et al.  Ldb1 is essential for development of Nkx2.1 lineage derived GABAergic and cholinergic neurons in the telencephalon. , 2014, Developmental biology.

[17]  Laura E. DeMare,et al.  Chromatin state signatures associated with tissue-specific gene expression and enhancer activity in the embryonic limb , 2012, Genome research.

[18]  M. Álvarez-Dolado,et al.  Dlx-Dependent and -Independent Regulation of Olfactory Bulb Interneuron Differentiation , 2007, The Journal of Neuroscience.

[19]  D. Tautz,et al.  A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns , 2010, Nature.

[20]  Ariel S. Schwartz,et al.  An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man , 2010, Cell.

[21]  Axel Visel,et al.  Functional autonomy of distant-acting human enhancers. , 2009, Genomics.

[22]  Lior Pachter,et al.  VISTA: computational tools for comparative genomics , 2004, Nucleic Acids Res..

[23]  J. Doudna,et al.  A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity , 2012, Science.

[24]  S. Anderson,et al.  Postmitotic Nkx2-1 Controls the Migration of Telencephalic Interneurons by Direct Repression of Guidance Receptors , 2008, Neuron.

[25]  Allan R. Jones,et al.  A mesoscale connectome of the mouse brain , 2014, Nature.

[26]  Wouter de Laat,et al.  A Regulatory Archipelago Controls Hox Genes Transcription in Digits , 2011, Cell.

[27]  S. Pääbo,et al.  Accelerated Evolution of Conserved Noncoding Sequences in Humans , 2006, Science.

[28]  S. Aizawa,et al.  Otx2 expression in anterior neuroectoderm and forebrain/midbrain is directed by more than six enhancers. , 2014, Developmental biology.

[29]  S. Brenner,et al.  Distinct cis-essential modules direct the time-space pattern of the Pax6 gene activity. , 1999, Developmental biology.

[30]  J. Rubenstein,et al.  NPAS1 Represses the Generation of Specific Subtypes of Cortical Interneurons , 2014, Neuron.

[31]  Shen-Ju Chou,et al.  Area Patterning of the Mammalian Cortex , 2007, Neuron.

[32]  Wei Niu,et al.  Coexpression Networks Implicate Human Midfetal Deep Cortical Projection Neurons in the Pathogenesis of Autism , 2013, Cell.

[33]  Allan R. Jones,et al.  Transcriptional Landscape of the Prenatal Human Brain , 2014, Nature.

[34]  M. Ekker,et al.  Distinct cis-Regulatory Elements from the Dlx1/Dlx2 Locus Mark Different Progenitor Cell Populations in the Ganglionic Eminences and Different Subtypes of Adult Cortical Interneurons , 2007, The Journal of Neuroscience.

[35]  Jay Shendure,et al.  Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations , 2012, Nature Genetics.

[36]  V. van Heyningen,et al.  PAX6 in sensory development. , 2002, Human molecular genetics.

[37]  G. Mandel,et al.  REST and Its Corepressors Mediate Plasticity of Neuronal Gene Chromatin throughout Neurogenesis , 2005, Cell.

[38]  G. Fishell,et al.  Directed Migration of Cortical Interneurons Depends on the Cell-Autonomous Action of Sip1 , 2013, Neuron.

[39]  S. Krauss,et al.  Forebrain-specific promoter/enhancer D6 derived from the mouse Dach1 gene controls expression in neural stem cells , 2002, Neuroscience.

[40]  N. Kessaris,et al.  LIM homeodomain transcription factor-dependent specification of bipotential MGE progenitors into cholinergic and GABAergic striatal interneurons , 2009, Development.

[41]  Jens Hjerling-Leffler,et al.  The Cell-Intrinsic Requirement of Sox6 for Cortical Interneuron Development , 2009, Neuron.

[42]  S. Anderson,et al.  NKX2.1 specifies cortical interneuron fate by activating Lhx6 , 2008, Development.

[43]  A. Visel,et al.  ChIP-Seq identification of weakly conserved heart enhancers , 2010, Nature Genetics.

[44]  A. Visel,et al.  Dlx1&2-Dependent Expression of Zfhx1b (Sip1, Zeb2) Regulates the Fate Switch between Cortical and Striatal Interneurons , 2013, Neuron.

[45]  A. Visel,et al.  ChIP-seq accurately predicts tissue-specific activity of enhancers , 2009, Nature.

[46]  J. Rossant,et al.  Inducible expression of an hsp68-lacZ hybrid gene in transgenic mice. , 1989, Development.

[47]  W. Dobyns,et al.  Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans , 2002, Nature Genetics.

[48]  J. Sebat,et al.  Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia , 2011, Nature.

[49]  D. Wilkin,et al.  Neuron , 2001, Brain Research.

[50]  J. Rubenstein,et al.  The Progenitor Zone of the Ventral Medial Ganglionic Eminence Requires Nkx2-1 to Generate Most of the Globus Pallidus But Few Neocortical Interneurons , 2010, The Journal of Neuroscience.

[51]  D. Eisenstat,et al.  Identification of a direct Dlx homeodomain target in the developing mouse forebrain and retina by optimization of chromatin immunoprecipitation. , 2004, Nucleic acids research.

[52]  L. Stubbs,et al.  Differences in human and chimpanzee gene expression patterns define an evolving network of transcription factors in brain , 2009, Proceedings of the National Academy of Sciences.

[53]  J. Noebels,et al.  Interneuron, interrupted: molecular pathogenesis of ARX mutations and X-linked infantile spasms , 2012, Current Opinion in Neurobiology.

[54]  Richard Bonneau,et al.  FIREWACh: High-throughput Functional Detection of Transcriptional Regulatory Modules in Mammalian Cells , 2014, Nature Methods.

[55]  M. Rieder,et al.  Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations , 2011, Nature Genetics.

[56]  Inna Dubchak,et al.  VISTA Enhancer Browser—a database of tissue-specific human enhancers , 2006, Nucleic Acids Res..

[57]  T. Meehan,et al.  An atlas of active enhancers across human cell types and tissues , 2014, Nature.

[58]  Y. Yanagawa,et al.  Lhx6 Activity Is Required for the Normal Migration and Specification of Cortical Interneuron Subtypes , 2007, The Journal of Neuroscience.

[59]  Gord Fishell,et al.  The genetics of early telencephalon patterning: some assembly required , 2008, Nature Reviews Neuroscience.

[60]  R. Young,et al.  Histone H3K27ac separates active from poised enhancers and predicts developmental state , 2010, Proceedings of the National Academy of Sciences.

[61]  C. Doe,et al.  Temporal fate specification and neural progenitor competence during development , 2013, Nature Reviews Neuroscience.

[62]  S. Batzoglou,et al.  Distribution and intensity of constraint in mammalian genomic sequence. , 2005, Genome research.

[63]  ENCODEConsortium,et al.  An Integrated Encyclopedia of DNA Elements in the Human Genome , 2012, Nature.

[64]  Simon C. Potter,et al.  Genome-wide Association Analysis Identifies 14 New Risk Loci for Schizophrenia , 2013, Nature Genetics.

[65]  B. Cohen,et al.  Massively parallel in vivo enhancer assay reveals that highly local features determine the cis-regulatory function of ChIP-seq peaks , 2013, Proceedings of the National Academy of Sciences.

[66]  Dustin E. Schones,et al.  Global analysis of the insulator binding protein CTCF in chromatin barrier regions reveals demarcation of active and repressive domains. , 2008, Genome research.

[67]  Allan R. Jones,et al.  A High-Resolution Spatiotemporal Atlas of Gene Expression of the Developing Mouse Brain , 2014, Neuron.

[68]  Hunter B. Fraser,et al.  Differences in enhancer activity in mouse and zebrafish reporter assays are often associated with changes in gene expression , 2012, BMC Genomics.

[69]  H. Shim,et al.  Gene targeting in mouse embryos mediated by RecA and modified single-stranded oligonucleotides , 2008, In Vitro Cellular & Developmental Biology - Animal.

[70]  E. Berry-Kravis,et al.  Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond , 2012, Neuropsychopharmacology.

[71]  J. Kleinman,et al.  Spatiotemporal transcriptome of the human brain , 2011, Nature.

[72]  L. Siever,et al.  Spatial and Temporal Mapping of De Novo Mutations in Schizophrenia to a Fetal Prefrontal Cortical Network , 2013, Cell.

[73]  T. Nieus,et al.  Frontiers in Cellular Neuroscience Cellular Neuroscience , 2022 .

[74]  H. Kiyonari,et al.  Regulation of Otx2 expression and its functions in mouse forebrain and midbrain , 2004, Development.

[75]  Michael D. Wilson,et al.  Cooperativity and Rapid Evolution of Cobound Transcription Factors in Closely Related Mammals , 2013, Cell.

[76]  S. V. van Heeringen,et al.  Dynamics of enhancer chromatin signatures mark the transition from pluripotency to cell specification during embryogenesis , 2012, Genome research.

[77]  James E. DiCarlo,et al.  RNA-Guided Human Genome Engineering via Cas9 , 2013, Science.

[78]  J. Rubenstein,et al.  Lhx6 Directly Regulates Arx and CXCR7 to Determine Cortical Interneuron Fate and Laminar Position , 2014, Neuron.

[79]  H. Zoghbi,et al.  Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2 , 1999, Nature Genetics.

[80]  J. Rubenstein,et al.  Dlx1 and Dlx2 Control Neuronal versus Oligodendroglial Cell Fate Acquisition in the Developing Forebrain , 2007, Neuron.

[81]  S. Hyman,et al.  Progress in the Genetics of Polygenic Brain Disorders: Significant New Challenges for Neurobiology , 2013, Neuron.

[82]  Y. Ruan,et al.  ChIP‐based methods for the identification of long‐range chromatin interactions , 2009, Journal of cellular biochemistry.

[83]  E. Liu,et al.  An Oestrogen Receptor α-bound Human Chromatin Interactome , 2009, Nature.

[84]  P. Rakic.  Specification of cerebral cortical areas. , 1988, Science.

[85]  John L.R. Rubenstein,et al.  Patterning and Cell Type Specification in the Developing CNS and PNS , 2013 .

[86]  S. Potter,et al.  The Zinc Finger Transcription Factor Sp8 Regulates the Generation and Diversity of Olfactory Bulb Interneurons , 2006, Neuron.

[87]  Michael Levine,et al.  Mechanisms of transcriptional precision in animal development. , 2012, Trends in genetics : TIG.

[88]  Charles Y. Lin,et al.  Discovery and characterization of super-enhancer-associated dependencies in diffuse large B cell lymphoma. , 2013, Cancer cell.

[89]  U. Rüther,et al.  Wnt and Bmp signalling cooperatively regulate graded Emx2 expression in the dorsal telencephalon. , 2002, Development.

[90]  Hongkui Zeng,et al.  Transcriptional Regulation of Enhancers Active in Protodomains of the Developing Cerebral Cortex , 2014, Neuron.

[91]  M. King,et al.  Evolution at two levels in humans and chimpanzees. , 1975, Science.

[92]  I. Cobos,et al.  Dlx Transcription Factors Promote Migration through Repression of Axon and Dendrite Growth , 2007, Neuron.

[93]  P. Arlotta,et al.  Specification of Cortical Projection Neurons , 2013 .

[94]  Mingfeng Li,et al.  Temporal Specification and Bilaterality of Human Neocortical Topographic Gene Expression , 2014, Neuron.

[95]  J. Rubenstein,et al.  Loss of Gsx1 and Gsx2 Function Rescues Distinct Phenotypes in Dlx1/2 Mutants , 2012, The Journal of comparative neurology.

[96]  R. Schwartz,et al.  Building the heart piece by piece: modularity of cis-elements regulating Nkx2-5 transcription. , 1999, Development.

[97]  Shiaoching Gong,et al.  A gene expression atlas of the central nervous system based on bacterial artificial chromosomes , 2003, Nature.

[98]  M. King,et al.  Genetic Heterogeneity in Human Disease , 2010, Cell.

[99]  Tanita Casci.  Development: Hourglass theory gets molecular approval , 2011, Nature Reviews Genetics.

[100]  T. Mikkelsen,et al.  Systematic dissection of regulatory motifs in 2000 predicted human enhancers using a massively parallel reporter assay. , 2013, Genome research.

[101]  David Haussler,et al.  Forces Shaping the Fastest Evolving Regions in the Human Genome , 2006, PLoS genetics.

[102]  Bing Ren,et al.  Fine Tuning of Craniofacial Morphology by Distant-Acting Enhancers , 2013, Science.

[103]  William Stafford Noble,et al.  Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project , 2007, Nature.

[104]  J. Rubenstein,et al.  Inactivation of Arx, the Murine Ortholog of the X-Linked Lissencephaly with Ambiguous Genitalia Gene, Leads to Severe Disorganization of the Ventral Telencephalon with Impaired Neuronal Migration and Differentiation , 2007, The Journal of Neuroscience.

[105]  Laura E. DeMare,et al.  The Evolution of Lineage-Specific Regulatory Activities in the Human Embryonic Limb , 2013, Cell.

[106]  L. Duret,et al.  Comment on "Human-Specific Gain of Function in a Developmental Enhancer" , 2009, Science.

[107]  S. R. Cajal.  Textura del Sistema Nervioso del Hombre y de los Vertebrados, 1899–1904 , 2019 .

[108]  S. Horvath,et al.  Transcriptomic Analysis of Autistic Brain Reveals Convergent Molecular Pathology , 2011, Nature.

[109]  Alessandra Pierani,et al.  Developmental Origin of the Neuronal Subtypes That Comprise the Amygdalar Fear Circuit in the Mouse , 2010, The Journal of Neuroscience.

[110]  J. Rubenstein,et al.  Dlx6 regulates molecular properties of the striatum and central nucleus of the amygdala , 2011, The Journal of comparative neurology.

[111]  Y. Yanagawa,et al.  Three human ARX mutations cause the lissencephaly-like and mental retardation with epilepsy-like pleiotropic phenotypes in mice. , 2009, Human molecular genetics.

[112]  Jonathan K. Pritchard,et al.  The Functional Consequences of Variation in Transcription Factor Binding , 2013, PLoS genetics.

[113]  R. Shah.  Optimization of chromatin immunoprecipitation , 2012 .

[114]  A. Visel,et al.  Response to Comment on "Human-Specific Gain of Function in a Developmental Enhancer" , 2009, Science.

[115]  D. Gifford,et al.  Tissue-specific transcriptional regulation has diverged significantly between human and mouse , 2007, Nature Genetics.

[116]  M. Nóbrega,et al.  Scanning Human Gene Deserts for Long-Range Enhancers , 2003, Science.

[117]  D. Odom,et al.  Evolution of transcription factor binding in metazoans — mechanisms and functional implications , 2014, Nature Reviews Genetics.

[118]  Matthew D. Schultz,et al.  Global Epigenomic Reconfiguration During Mammalian Brain Development , 2013, Science.

[119]  Michael D. Wilson,et al.  Five-Vertebrate ChIP-seq Reveals the Evolutionary Dynamics of Transcription Factor Binding , 2010, Science.

[120]  J. Rubenstein,et al.  Bidirectional homeostatic plasticity induced by interneuron cell death and transplantation in vivo , 2013, Proceedings of the National Academy of Sciences.

[121]  J. Joung,et al.  Locus-specific editing of histone modifications at endogenous enhancers using programmable TALE-LSD1 fusions , 2013, Nature Biotechnology.

[122]  John H. Krystal,et al.  Psychiatric Disorders: Diagnosis to Therapy , 2014, Cell.

[123]  A. Visel,et al.  Rapid and Pervasive Changes in Genome-wide Enhancer Usage during Mammalian Development , 2013, Cell.

[124]  W. Sung,et al.  Chromatin connectivity maps reveal dynamic promoter–enhancer long-range associations , 2013, Nature.

[125]  P. Arlotta,et al.  Neuronal subtype specification in the cerebral cortex , 2007, Nature Reviews Neuroscience.

[126]  Leyuan Shi,et al.  Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. , 1997, Science.

[127]  S. Anderson,et al.  NKX 2 . 1 specifies cortical interneuron fate by activating Lhx 6 , 2022 .

[128]  D. Haussler,et al.  Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. , 2005, Genome research.

[129]  J. Rubenstein,et al.  Distinct molecular pathways for development of telencephalic interneuron subtypes revealed through analysis of Lhx6 mutants , 2008, The Journal of comparative neurology.

[130]  M. Ekker,et al.  Generation of Cre-transgenic mice using Dlx1/Dlx2 enhancers and their characterization in GABAergic interneurons , 2009, Molecular and Cellular Neuroscience.

[131]  Ryan A. Flynn,et al.  A unique chromatin signature uncovers early developmental enhancers in humans , 2011, Nature.

[132]  Nadav Ahituv,et al.  Function and Regulation of AUTS2, a Gene Implicated in Autism and Human Evolution , 2013, PLoS genetics.

[133]  D. Geschwind,et al.  Human-Specific Transcriptional Regulation of CNS Development Genes by FOXP2 , 2009, Nature.

[134]  M. Perry,et al.  Inducible expression of an hsp 68-lacZ hybrid gene in transgenic mice , 2005 .

[135]  M. Calcagnotto,et al.  Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy , 2005, Nature Neuroscience.

[136]  B. Oostra,et al.  A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. , 2003, Human molecular genetics.

[137]  I. Amit,et al.  Comprehensive mapping of long range interactions reveals folding principles of the human genome , 2011 .

[138]  Philip L. F. Johnson,et al.  A Draft Sequence of the Neandertal Genome , 2010, Science.

[139]  Shane J. Neph,et al.  Developmental Fate and Cellular Maturity Encoded in Human Regulatory DNA Landscapes , 2013, Cell.

[140]  Winnie S. Liang,et al.  Dlx1&2 and Mash1 transcription factors control striatal patterning and differentiation through parallel and overlapping pathways , 2009, The Journal of comparative neurology.

[141]  J. Sutcliffe,et al.  Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome , 1991, Cell.

[142]  J. Rubenstein,et al.  Olig1 Function Is Required to Repress Dlx1/2 and Interneuron Production in Mammalian Brain , 2014, Neuron.

[143]  Joseph B Hiatt,et al.  Massively parallel functional dissection of mammalian enhancers in vivo , 2012, Nature Biotechnology.

[144]  Berthold Göttgens,et al.  Function-based Identification of Mammalian Enhancers Using Site-Specific Integration , 2014, Nature Methods.

[145]  E. Eichler,et al.  Regional patterns of gene expression in human and chimpanzee brains. , 2004, Genome research.

[146]  Alan M. Moses,et al.  In vivo enhancer analysis of human conserved non-coding sequences , 2006, Nature.

[147]  Vasily M. Studitsky,et al.  Distant Activation of Transcription: Mechanisms of Enhancer Action , 2012, Molecular and Cellular Biology.

[148]  J. Keith Joung,et al.  Interactome Maps of Mouse Gene Regulatory Domains Reveal Basic Principles of Transcriptional Regulation , 2013, Cell.

[149]  A. Visel,et al.  Use of “MGE Enhancers” for Labeling and Selection of Embryonic Stem Cell-Derived Medial Ganglionic Eminence (MGE) Progenitors and Neurons , 2013, PloS one.

[150]  Axel Visel,et al.  Deletion of Ultraconserved Elements Yields Viable Mice , 2007, PLoS biology.

[151]  Bradley P. Coe,et al.  Multiplex Targeted Sequencing Identifies Recurrently Mutated Genes in Autism Spectrum Disorders , 2012, Science.

[152]  J. Rubenstein,et al.  Arx Is a Direct Target of Dlx2 and Thereby Contributes to the Tangential Migration of GABAergic Interneurons , 2008, The Journal of Neuroscience.

[153]  David A. Orlando,et al.  Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes , 2013, Cell.

[154]  Long Gao,et al.  Discover context-specific combinatorial transcription factor interactions by integrating diverse ChIP-Seq data sets , 2013, Nucleic acids research.

[155]  S. Horvath,et al.  Integrative Functional Genomic Analyses Implicate Specific Molecular Pathways and Circuits in Autism , 2013, Cell.

[156]  S. Christian,et al.  Targeted loss of Arx results in a developmental epilepsy mouse model and recapitulates the human phenotype in heterozygous females. , 2009, Brain : a journal of neurology.

[157]  H. Lai,et al.  bHLH factors in neurogenesis and neuronal subtype specification , 2013, Patterning and Cell Type Specification in the Developing CNS and PNS.

[158]  M. Ekker,et al.  A Highly Conserved Enhancer in the Dlx5/Dlx6Intergenic Region is the Site of Cross-Regulatory Interactions betweenDlx Genes in the Embryonic Forebrain , 2000, The Journal of Neuroscience.

[159]  Data production leads,et al.  An integrated encyclopedia of DNA elements in the human genome , 2012 .

[160]  S. Anderson,et al.  Mutations of the Homeobox Genes Dlx-1 and Dlx-2 Disrupt the Striatal Subventricular Zone and Differentiation of Late Born Striatal Neurons , 1997, Neuron.

[161]  Hani Z. Girgis,et al.  A High-Resolution Enhancer Atlas of the Developing Telencephalon , 2013, Cell.

[162]  A. Sandelin,et al.  Metazoan promoters: emerging characteristics and insights into transcriptional regulation , 2012, Nature Reviews Genetics.

[163]  D. Hill,et al.  Gene and enhancer trapping: mutagenic strategies for developmental studies. , 1993, Current topics in developmental biology.

[164]  Oscar Marín,et al.  The LIM-homeobox gene Lhx8 is required for the development of many cholinergic neurons in the mouse forebrain , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[165]  S. Aizawa,et al.  The same enhancer regulates the earliest Emx2 expression in caudal forebrain primordium, subsequent expression in dorsal telencephalon and later expression in the cortical ventricular zone , 2010, Development.

[166]  C. Schreiner,et al.  Chronic reduction in inhibition reduces receptive field size in mouse auditory cortex , 2012, Proceedings of the National Academy of Sciences.

[167]  Avinash Bhandoola,et al.  Faculty Opinions recommendation of In vivo genome editing using a high-efficiency TALEN system. , 2013 .

[168]  J. Rubenstein,et al.  Pyramidal Neurons in Prefrontal Cortex Receive Subtype-Specific Forms of Excitation and Inhibition , 2014, Neuron.

[169]  G. Stamatoyannopoulos.  Control of globin gene expression during development and erythroid differentiation. , 2005, Experimental hematology.

[170]  I. Cobos,et al.  Dlx1&2 and Mash1 transcription factors control MGE and CGE patterning and differentiation through parallel and overlapping pathways. , 2009, Cerebral cortex.

[171]  J. Tena,et al.  Identification and Analysis of Conserved cis-Regulatory Regions of the MEIS1 Gene , 2012, PloS one.

[172]  Dave T. Gerrard,et al.  Gene expression divergence recapitulates the developmental hourglass model , 2010, Nature.

[173]  A. Stark,et al.  Transcriptional enhancers: from properties to genome-wide predictions , 2014, Nature Reviews Genetics.

[174]  J. Shendure,et al.  Massively parallel decoding of mammalian regulatory sequences supports a flexible organizational model , 2013, Nature Genetics.

[175]  Wei Wu,et al.  From neural development to cognition: unexpected roles for chromatin , 2013, Nature Reviews Genetics.

[176]  J. Rubenstein,et al.  Modulation of the notch signaling by Mash1 and Dlx1/2 regulates sequential specification and differentiation of progenitor cell types in the subcortical telencephalon. , 2002, Development.

[177]  Bradley P. Coe,et al.  Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations , 2012, Nature.

[178]  J. Rubenstein,et al.  Neurogenesis in the basal ganglia , 2020, Patterning and Cell Type Specification in the Developing CNS and PNS.

[179]  Cory Y. McLean,et al.  Human-specific loss of regulatory DNA and the evolution of human-specific traits , 2011, Nature.

[180]  Erin L. Doyle,et al.  Targeting DNA Double-Strand Breaks with TAL Effector Nucleases , 2010, Genetics.

[181]  Harris Morrison,et al.  Enhancer‐adoption as a mechanism of human developmental disease , 2011, Human mutation.

[182]  Stephen C. J. Parker,et al.  Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants , 2013, Proceedings of the National Academy of Sciences.

[183]  J. Sebat,et al.  Duplications of the Neuropeptide Receptor VIPR2 Confer Significant Risk for Schizophrenia , 2011, Nature.

[184]  K. Deisseroth,et al.  Dlx5 and Dlx6 Regulate the Development of Parvalbumin-Expressing Cortical Interneurons , 2010, The Journal of Neuroscience.

[185]  I. Grosse,et al.  A transcriptomic hourglass in plant embryogenesis , 2012, Nature.

[186]  Veronique Lefebvre,et al.  Cis-regulatory control of corticospinal system development and evolution , 2012, Nature.

[187]  Bernardo Rudy,et al.  Satb1 Is an Activity-Modulated Transcription Factor Required for the Terminal Differentiation and Connectivity of Medial Ganglionic Eminence-Derived Cortical Interneurons , 2012, The Journal of Neuroscience.

[188]  Lee E. Edsall,et al.  A map of the cis-regulatory sequences in the mouse genome , 2012, Nature.

[189]  M. Depew,et al.  DLX5 Regulates Development of Peripheral and Central Components of the Olfactory System , 2003, The Journal of Neuroscience.

[190]  O. Marín,et al.  Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum. , 1999, Development.

[191]  Alexander Schleiffer,et al.  Combinatorial Activation and Repression by Seven Transcription Factors Specify Drosophila Odorant Receptor Expression , 2012, PLoS biology.

[192]  Philip Cayting,et al.  An encyclopedia of mouse DNA elements (Mouse ENCODE) , 2012, Genome Biology.

[193]  Margaret B. Fish,et al.  Disruption of autoregulatory feedback by a mutation in a remote, ultraconserved PAX6 enhancer causes aniridia. , 2013, American journal of human genetics.

[194]  F. Guillemot,et al.  A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets. , 2011, Genes & development.

[195]  Barbara Clancy,et al.  Extrapolating brain development from experimental species to humans. , 2007, Neurotoxicology.

[196]  R. Favaro,et al.  Emx2 is a dose-dependent negative regulator of Sox2 telencephalic enhancers , 2012, Nucleic acids research.

[197]  Bradley E. Bernstein,et al.  Genome-wide Chromatin State Transitions Associated with Developmental and Environmental Cues , 2013, Cell.

[198]  R. Young,et al.  Super-Enhancers in the Control of Cell Identity and Disease , 2013, Cell.

[199]  M. Ekker,et al.  An SNP in an ultraconserved regulatory element affects Dlx5/Dlx6 regulation in the forebrain , 2010, Development.

[200]  M. Denaxa,et al.  Maturation-Promoting Activity of SATB1 in MGE-Derived Cortical Interneurons , 2012, Cell reports.

[201]  G. Fishell,et al.  The generation of cortical interneurons , 2013, Patterning and Cell Type Specification in the Developing CNS and PNS.