CoChat
Sign Up
Cited by 110Genetics and Neurodevelopmental DisordersAutism Spectrum Disorder ResearchSingle-cell and spatial transcriptomics

The developmental transcriptome of the human brain: implications for neurodevelopmental disorders

Open access
Tebbenkamp, Andrew T.N., Willsey, A. Jeremy, State, Matthew W., Šestan, Nenad·2014·Current Opinion in Neurology
DOI 10.1097/wco.0000000000000069PMC PMC4038354
Open this paper in CoChat — free account

Abstract

PURPOSE OF REVIEW: Recent characterizations of the transcriptome of the developing human brain by several groups have generated comprehensive datasets on coding and noncoding RNAs that will be instrumental for illuminating the underlying biology of complex neurodevelopmental disorders. This review summarizes recent studies successfully utilizing these data to increase our understanding of the molecular mechanisms of pathogenesis. RECENT FINDINGS: Several approaches have successfully integrated developmental transcriptome data with gene discovery to generate testable hypotheses about when and where in the developing human brain disease-associated genes converge. Specifically, these include the projection neurons in the prefrontal and primary motor--somatosensory cortex during mid-fetal development in autism spectrum disorder and the frontal cortex during fetal development in schizophrenia. SUMMARY: Developmental transcriptome data is a key to interpreting disease-associated mutations and transcriptional changes. Novel approaches integrating the spatial and temporal dimensions of these data have increased our understanding of when and where disease occurs. Refinement of spatial and temporal properties and expanding these findings to other neurodevelopmental disorders will provide critical insights for understanding disease biology.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1097/wco.0000000000000069

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • DFC and CBC were chosen for analyses because both regions have been implicated in DS neuropathology and exhibit diverse transcriptional profiles over development.

    “We chose dorsal frontal cortex (DFC) and CBC for our analyses because both regions have been implicated in DS neuropathology (Hartley et al., 2014; Haydar and Reeves, 2012; Letourneau et al., 2014; Lott, 2012) and exhibit diverse transcriptional profiles over the course of development (Kang et al., 2011; Tebbenkamp et al., 2014).”

    From Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination (2016) · cites this paper as Tebbenkamp et al., 2014

    The Introduction describes dynamic gene expression during human brain development and links expression patterns to regional specialization. The Autism spectrum disorders section discusses the frontal neocortex and cerebellum, but does not establish that both specifically exhibit diverse transcriptional profiles over development. The Down syndrome neuropathology rationale is attached to other citations, not Tebbenkamp et al. (LLM, conf=0.81)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 51 · Cited by 110

Research works printed but not linked: 35

  1. [1]Johnson MB Kawasawa YI Mason CE Krsnik Z Coppola G Bogdanovic D Functional and evolutionary insights into human brain development through global transcriptome analysis Neuron 2009 62 494 509 19477152 PMC2739738
  2. [2]Somel M Franz H Yan Z Lorenc A Guo S Giger T Transcriptional neoteny in the human brain Proc Natl Acad Sci U S A 2009 106 5743 5748 19307592 PMC2659716
  3. [3]Ip BK Wappler I Peters H Lindsay S Clowry GJ Bayatti N Investigating gradients of gene expression involved in early human cortical development J Anat 2010 217 300 311 20579172 PMC2992409
  4. [4]Colantuoni C Lipska BK Ye T Hyde TM Tao R Leek JT Temporal dynamics and genetic control of transcription in the human prefrontal cortex Nature 478 519 523 201 22031444 PMC3510670
  5. [5]Kang HJ Kawasawa YI Cheng F Zhu Y Xu X Li M Spatio-temporal transcriptome of the human brain Nature 478 483 489 201 22031440 PMC3566780
  6. [7]Hawrylycz MJ Lein ES Guillozet-Bongaarts AL Shen EH Ng L Miller JA An anatomically comprehensive atlas of the adult human brain transcriptome Nature 2012 489 391 399 22996553 PMC4243026
  7. [9]Pletikos M Sousa AM Sedmak G Meyer KA Zhu Y Cheng F Temporal specification and bilaterality of human neocortical topographic gene expression Neuron 2014 in press. PMC3931000 24373884
  8. [10]Iossifov I Ronemus M Levy D Wang Z Hakker I Rosenbaum J De novo gene disruptions in children on the autistic spectrum Neuron 2012 74 285 299 22542183 PMC3619976
  9. [11]Kong A Frigge ML Masson G Besenbacher S Sulem P Magnusson G Rate of de novo mutations and the importance of father's age to disease risk Nature 2012 488 471 475 22914163 PMC3548427
  10. [13]Sanders SJ Ercan-Sencicek AG Hus V Luo R Murtha MT Moreno-De-Luca D Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism Neuron 2011 70 863 885 21658581 PMC3939065
  11. [15]Sanders SJ Murtha MT Gupta AR Murdoch JD Raubeson MJ Willsey AJ De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485 237 241 22495306 PMC3667984
  12. [21]Kwan KY Lam MM Johnson MB Dube U Shim S Rasin MR Species-dependent posttranscriptional regulation of NOS1 by FMRP in the developing cerebral cortex Cell 2012 149 899 911 22579290 PMC3351852
  13. [22]Dolmetsch R Geschwind DH The human brain in a dish: the promise of iPSC-derived neurons Cell 2011 145 831 834 21663789 PMC3691069
  14. [23]Griesi-Oliveira K Sunaga DY Alvizi L Vadasz E Passos-Bueno MR Stem cells as a good tool to investigate dysregulated biological systems in autism spectrum disorders Autism Res 2013 6 354 361 23801657
  15. [24]Smith RM Sadee W Synaptic signaling and aberrant RNA splicing in autism spectrum disorders Front Synaptic Neurosci 2011 3 1 21423409 PMC3059609
  16. [26]Weiss LA Shen Y Korn JM Arking DE Miller DT Fossdal R Association between microdeletion and microduplication at 16p11.2 and autism N Engl J Med 2008 358 667 675 18184952
  17. [27]Glessner JT Wang K Cai G Korvatska O Kim CE Wood S Autism genome-wide copy number variation reveals ubiquitin and neuronal genes Nature 2009 459 569 573 19404257 PMC2925224
  18. [31]Szatmari P Paterson AD Zwaigenbaum L Roberts W Brian J Liu XQ Mapping autism risk loci using genetic linkage and chromosomal rearrangements Nat Genet 2007 39 319 328 17322880 PMC4867008
  19. [32]Luo R Sanders SJ Tian Y Voineagu I Huang N Chu SH Genome-wide transcriptome profiling reveals the functional impact of rare de novo and recurrent CNVs in autism spectrum disorders Am J Hum Genet 2012 91 38 55 22726847 PMC3397271
  20. [33]Ben-David E Shifman S Combined analysis of exome sequencing points toward a major role for transcription regulation during brain development in autism Mol Psychiatry 2013 18 1054 1056 23147383 ** This study used publicly available BrainSpan data to construct co-expression networks with ASD genes and found enrichment for chromatin modifiers, which was independently supported by whole exome sequencing efforts.
  21. [34]Willsey AJ Sanders SJ Li M Dong S Tebbenkamp AT Muhle RA Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism Cell 2013 155 997 1007 24267886 PMC3995413 ** This study implicated deep layer cortical projection neurons in prefrontal and primary motor-somatosensory cortical regions during mid-fetal development via construction of spatio-temporal gene co-expression networks around autism genes identified with whole-exome sequencing.
  22. [35]Gulsuner S Walsh T Watts AC Lee MK Thornton AM Casadei S Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network Cell 2013 154 518 529 23911319 PMC3894107 ** This study identified a network of putative schizophrenia risk genes that are highly co-expressed in fetal prefrontal cortex
  23. [36]Parikshak NN Luo R Zhang A Won H Lowe JK Chandran V Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism Cell 2013 155 1008 1021 24267887 PMC3934107 ** This study utilized weighted gene co-expression network analysis and autism risk genes to identify modules of co-expressed genes preferentially expressed in superficial cortical projection neurons.
  24. [37]Mulle JG Pulver AE McGrath JA Wolyniec PS Dodd AF Cutler DJ Reciprocal duplication of the Williams-Beuren syndrome deletion on chromosome 7q11.23 Is associated with schizophrenia Biol Psychiatry 2013 S0006-3223(13)00527-1 PMC3838485 23871472
  25. [38]Antonell A Vilardell M Perez Jurado LA Transcriptome profile in Williams-Beuren syndrome lymphoblast cells reveals gene pathways implicated in glucose intolerance and visuospatial construction deficits Hum Genet 2010 128 27 37 20401492
  26. [39]Henrichsen CN Csardi G Zabot MT Fusco C Bergmann S Merla G Using transcription modules to identify expression clusters perturbed in Williams-Beuren syndrome PLoS Comput Biol 2011 7 e1001054 21304579 PMC3024257
  27. [40]Drummond JB Simmons M Haroutunian V Meador-Woodruff JH Upregulation of cornichon transcripts in the dorsolateral prefrontal cortex in schizophrenia Neuroreport 2012 23 1031 1034 23103966
  28. [41]Tao R Li C Newburn EN Ye T Lipska BK Herman MM Transcript-specific associations of SLC12A5 (KCC2) in human prefrontal cortex with development, schizophrenia, and affective disorders J Neurosci 2012 32 5216 5222 22496567 PMC3752043
  29. [42]Habl G Schmitt A Zink M von Wilmsdorff M Yeganeh-Doost P Jatzko A Decreased reelin expression in the left prefrontal cortex (BA9) in chronic schizophrenia patients Neuropsychobiology 2012 66 57 62 22797278
  30. [43]Perez-Santiago J Diez-Alarcia R Callado LF Zhang JX Chana G White CH A combined analysis of microarray gene expression studies of the human prefrontal cortex identifies genes implicated in schizophrenia J Psychiatr Res 2012 46 1464 1474 22954356
  31. [44]Mistry M Gillis J Pavlidis P Genome-wide expression profiling of schizophrenia using a large combined cohort Mol Psychiatry 2013 18 215 225 22212594 PMC3323740
  32. [45]Cohen OS McCoy SY Middleton FA Bialosuknia S Zhang-James Y Liu L Transcriptomic analysis of postmortem brain identifies dysregulated splicing events in novel candidate genes for schizophrenia Schizophr Res 2012 142 188 99 23062752 PMC3502694
  33. [46]Kahler AK Djurovic S Kulle B Jonsson EG Agartz I Hall H Association analysis of schizophrenia on 18 genes involved in neuronal migration: MDGA1 as a new susceptibility gene Am J Med Genet B Neuropsychiatr Genet 2008 147B 1089 1100 18384059
  34. [47]Wu JQ Wang X Beveridge NJ Tooney PA Scott RJ Carr VJ Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia PLoS One 2012 7 e36351 22558445 PMC3338678
  35. [50]Klei L Sanders SJ Murtha MT Hus V Lowe JK Willsey AJ Common genetic variants, acting additively, are a major source of risk for autism Mol Autism 2012 3 9 23067556 PMC3579743

Authors
Tebbenkamp, A. T. N., Willsey, A. J., State, M. W., & Šestan, N.
Affiliations
University of California, San Francisco (US)
Corresponding author
  • Tebbenkamp, Andrew T.N.
  • Willsey, A. Jeremy
ORCID
Venue
Current Opinion in Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2014-04
Volume
27
Issue
2
Pages
149-156
ISSN
1350-7540 (ISSN-L)
DOI
10.1097/wco.0000000000000069
PMC
PMC4038354
OpenAlex
W2058166388
Cited by
110
References
51
Citations by year
2026: 6 · 2025: 3 · 2024: 4 · 2023: 9 · 2022: 9 · 2021: 13 · 2020: 9 · 2019: 6 · 2018: 12 · 2017: 9 · 2016: 13 · 2015: 10 · 2014: 7
FWCI
1.72
Type
journal article
Language
en
Open access
Locations
  • Current Opinion in Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Canadian Institutes of Health Research
  • National Institute of Mental Health (RC2MH089956, MH081896, MH089956, U01MH081896)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
Keywords
human brain development, developmental transcriptome, neurodevelopmental disorders, autism spectrum disorder, schizophrenia, disease-associated genes, prefrontal cortex, projection neurons, fetal development, non-coding RNA, spatiotemporal gene expression
MeSH terms
Brain, Brain Diseases, Developmental Disabilities, Child Development Disorders, Pervasive, Humans, Schizophrenia, Gene Expression Regulation, Developmental, Williams Syndrome, Transcriptome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review