Brain Structure and Function

, Volume 220, Issue 5, pp 3053–3060

DUF1220 protein domains drive proliferation in human neural stem cells and are associated with increased cortical volume in anthropoid primates

  • J. G. Keeney
  • J. M. Davis
  • J. Siegenthaler
  • M. D. Post
  • B. S. Nielsen
  • W. D. Hopkins
  • J. M. Sikela
Short Communication

DOI: 10.1007/s00429-014-0814-9

Cite this article as:
Keeney, J.G., Davis, J.M., Siegenthaler, J. et al. Brain Struct Funct (2015) 220: 3053. doi:10.1007/s00429-014-0814-9

Abstract

Genome sequences encoding DUF1220 protein domains show a burst in copy number among anthropoid species and especially humans, where they have undergone the greatest human lineage-specific copy number expansion of any protein coding sequence in the genome. While DUF1220 copy number shows a dosage-related association with brain size in both normal populations and in 1q21.1-associated microcephaly and macrocephaly, a function for these domains has not yet been described. Here we provide multiple lines of evidence supporting the view that DUF1220 domains function as drivers of neural stem cell proliferation among anthropoid species including humans. First, we show that brain MRI data from 131 individuals across 7 anthropoid species shows a strong correlation between DUF1220 copy number and multiple brain size-related measures. Using in situ hybridization analyses of human fetal brain, we also show that DUF1220 domains are expressed in the ventricular zone and primarily during human cortical neurogenesis, and are therefore expressed at the right time and place to be affecting cortical brain development. Finally, we demonstrate that in vitro expression of DUF1220 sequences in neural stem cells strongly promotes proliferation. Taken together, these data provide the strongest evidence so far reported implicating DUF1220 dosage in anthropoid and human brain expansion through mechanisms involving increasing neural stem cell proliferation.

Keywords

DUF1220Neural stem cell proliferationBrain developmentHuman brainBrain sizeBrain evolution

Supplementary material

429_2014_814_MOESM1_ESM.docx (2.4 mb)
Supplementary material 1 (DOCX 2412 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • J. G. Keeney
    • 1
  • J. M. Davis
    • 1
  • J. Siegenthaler
    • 2
  • M. D. Post
    • 3
  • B. S. Nielsen
    • 4
  • W. D. Hopkins
    • 5
    • 6
  • J. M. Sikela
    • 1
  1. 1.Department of Biochemistry and Molecular Genetics and Human Medical Genetics and Neuroscience ProgramsUniversity of Colorado School of MedicineAuroraUSA
  2. 2.Section of Developmental Biology, Department of PediatricsUniversity of Colorado, DenverAuroraUSA
  3. 3.Department of PathologyUniversity of ColoradoAuroraUSA
  4. 4.Department of Molecular HistologyBioneer A/SHoersholmDenmark
  5. 5.Neuroscience InstituteGeorgia State UniversityAtlantaUSA
  6. 6.Division of Developmental and Cognitive NeuroscienceYerkes National Primate Research CenterAtlantaUSA