Anatomical, animal, and cellular evidence for Zika-induced pathogenesis of fetal microcephaly

  • Jing-Zhang Wang
    Corresponding author at: Department of Medical Technology, College of Medicine, Affiliated Hospital, Hebei University of Engineering, 81 or 83 Cong Tai Road, Handan 056002, Hebei Province, PR China. Fax: +86 0310 8575130.
    Hebei University of Engineering, Affiliated Hospital, College of Medicine, Handan 056002, Hebei Province, PR China
    Search for articles by this author
  • Xin-Hua Guo
    Hebei University of Engineering, Affiliated Hospital, College of Medicine, Handan 056002, Hebei Province, PR China
    Search for articles by this author
  • Dian-Guo Xu
    Hebei University of Engineering, Affiliated Hospital, College of Medicine, Handan 056002, Hebei Province, PR China
    Search for articles by this author
Published:November 19, 2016DOI:


      Several recent articles published by Brain and Development in 2016 demonstrated some rare, but innovative, genetic mechanisms for microcephaly. This concise mini-review presented another novel pathogenic mechanism for microcephaly, which has actually been a worldwide medical challenge since the World Health Organization (WHO) defined the outbreak of the Zika virus (ZIKV) as an International Public Health Emergency on 1 Feb, 2016. As a recent noteworthy clinical phenomenon, the ZIKV outbreak was accompanied by a dramatically increased number of microcephalus fetuses. However, no direct evidence supporting the suspected pathogenic effects of ZIKV on fetal microcephaly was shown previously before 2016. Herein, we evaluated the most important human pathological, animal developmental, and neuro-cytotoxic findings released in 2016, and highlighted the original experimental evidence that strengthens the potential link between ZIKV and the high incidence of microcephaly in new-born babies. Because killing mosquitoes via insecticides is currently the only effective way to suppress ZIKV-induced disorders, the animal and cellular models described in this mini-review are very beneficial to anti-ZIKV drug development and vaccine assessment.


      ZIKV (the Zika virus), CT (computed tomography), MRI (magnetic resonance imaging), IFN (interferon)


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Brain and Development
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Yilmaz S.
        • Gokben S.
        • Serdaroglu G.
        • Eraslan C.
        • Mancini G.M.S.
        • Tekin H.
        • et al.
        The expanding phenotypic spectrum of ARFGEF2 gene mutation: Cardiomyopathy and movement disorder.
        Brain Dev. 2016; 38: 124-127
        • Pinto A.M.
        • Bianciardi L.
        • Mencarelli M.A.
        • Imperatore V.
        • Di Marco C.
        • Furini S.
        • et al.
        Exome sequencing analysis in a pair of monozygotic twins re-evaluates the genetics behind their intellectual disability and reveals a CHD2 mutation.
        Brain Dev. 2016; 38: 590-596
        • Nozaki F.
        • Kusunoki T.
        • Okamoto N.
        • Yamamoto Y.
        • Miya F.
        • Tsunoda T.
        • et al.
        ALDH18A1-related cutis laxa syndrome with cyclic vomiting.
        Brain Dev. 2016; 38: 678-684
        • Asahina M.
        • Endoh Y.
        • Matsubayashi T.
        • Fukuda T.
        • Ogata T.
        Novel RAB3GAP1 compound heterozygous mutations in Japanese siblings with Warburg Micro syndrome.
        Brain Dev. 2016; 38: 337-340
        • Hirabayashi S.
        • Saitsu H.
        • Matsumoto N.
        Distinct but milder phenotypes with choreiform movements in siblings with compound heterozygous mutations in the transcription preinitiation mediator complex subunit 17 (MED17).
        Brain Dev. 2016; 38: 118-123
        • Cugola F.R.
        • Fernandes I.R.
        • Russo F.B.
        • Freitas B.C.
        • Dias J.L.M.
        • Guimaraes K.P.
        • et al.
        The Brazilian Zika virus strain causes birth defects in experimental models.
        Nature. 2016; 534: 267-271
        • Chang C.
        • Ortiz K.
        • Ansari A.
        • Gershwin M.E.
        The Zika outbreak of the 21st century.
        J Autoimmun. 2016; 68: 1-13
        • Mlakar J.
        • Korva M.
        • Tul N.
        • Popovic M.
        • Poljsak-Prijatelj M.
        • Mraz J.
        • et al.
        Zika virus associated with microcephaly.
        New Engl J Med. 2016; 374: 951-958
        • Faria N.R.
        • Azevedo R.D.D.
        • Kraemer M.U.G.
        • Souza R.
        • Cunha M.S.
        • Hill S.C.
        • et al.
        Zika virus in the Americas: early epidemiological and genetic findings.
        Science. 2016; 352: 345-349
        • Miner J.J.
        • Cao B.
        • Govero J.
        • Smith A.M.
        • Fernandez E.
        • Cabrera O.H.
        • et al.
        Zika virus infection during pregnancy in mice causes placental damage and fetal demise.
        Cell. 2016; 165: 1080-1091
        • Calvet G.
        • Aguiar R.S.
        • Melo A.S.O.
        • Sampaio S.A.
        • de Filippis I.
        • Fabri A.
        • et al.
        Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study.
        Lancet Infect Dis. 2016; 16: 653-660
        • England J.D.
        Editor’s update and selected articles from the Journal of the Neurological Sciences.
        J Neurol Sci. 2016; 366: 125-126
        • Dowall S.D.
        • Graham V.A.
        • Rayner E.
        • Atkinson B.
        • Hall G.
        • Watson R.J.
        • et al.
        A susceptible mouse model for Zika virus infection.
        Plos Negl Trop Dis. 2016; 10: e0004658
        • Qian X.Y.
        • Nguyen H.N.
        • Song M.M.
        • Hadiono C.
        • Ogden S.C.
        • Hammack C.
        • et al.
        Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure.
        Cell. 2016; 165: 1238-1254
        • Garcez P.P.
        • Loiola E.C.
        • Da Costa R.M.
        • Higa L.M.
        • Trindade P.
        • Delvecchio R.
        • et al.
        Zika virus impairs growth in human neurospheres and brain organoids.
        Science. 2016; 352: 816-818
        • Kostyuchenko V.A.
        • Lim E.X.Y.
        • Zhang S.J.
        • Fibriansah G.
        • Ng T.S.
        • Ooi J.S.G.
        • et al.
        Structure of the thermally stable Zika virus.
        Nature. 2016; 533: 425-428
        • Shimojima K.
        • Narai S.
        • Togawa M.
        • Doumoto T.
        • Sangu N.
        • Vanakker O.M.
        • et al.
        7p22.1 microdeletions involving ACTB associated with developmental delay, short stature, and microcephaly.
        Eur J Med Genet. 2016; 59: 502-506
        • Pavone P.
        • Pratico A.D.
        • Gentile G.
        • Falsaperla R.
        • Iemmolo R.
        • Guarnaccia M.
        • et al.
        A neurocutaneous phenotype with paired hypo- and hyperpigmented macules, microcephaly and stunted growth as prominent features.
        Eur J Med Genet. 2016; 59: 283-289
        • Milone R.
        • Valetto A.
        • Battini R.
        • Bertini V.
        • Valvo G.
        • Cioni G.
        • et al.
        Focal cortical dysplasia, microcephaly and epilepsy in a boy with 1q21.1-q21.3 duplication.
        Eur J Med Genet. 2016; 59: 278-282