Evidence map›Paper›PMID 31735666›Full record

ArticleDevelopmental cell2019

Mutations in ANKLE2, a ZIKA Virus Target, Disrupt an Asymmetric Cell Division Pathway in Drosophila Neuroblasts to Cause Microcephaly.

Nichole Link, Hyunglok Chung, Angad Jolly, Marjorie Withers, Burak Tepe, Benjamin R Arenkiel, Priya S Shah, Nevan J Krogan, Hatip Aydin, Bilgen B Geckinli and 9 more

Open access · bronzeAbstract read
In one paragraph

Article in Developmental cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
12.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

75 citing papers in PubMed, 113 citations in OpenAlex.

  1. Article
  2. Sequence and structural alignments reveal insights into ANKLE2 evolution and function.Protein science : a publication of the Protein Society · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Cells · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Asymmetry of centrosomes inMolecular biology of the cell · 2025
    Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. A novelFly · 2024
    Article
  19. Article
  20. Article

15 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 14 institutions in 2 countries.

Nichole LinkHoward Hughes Medical Institute, BCM, Houston, TX 77030, USA; Department of Molecular and Human Genetics, BCM, Houston, TX 77030, USA; Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.
Hyunglok ChungHoward Hughes Medical Institute, BCM, Houston, TX 77030, USA; Department of Molecular and Human Genetics, BCM, Houston, TX 77030, USA; Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.
Angad JollyDepartment of Molecular and Human Genetics, BCM, Houston, TX 77030, USA; MD/PhD Medical Scientist Training Program and MHG Graduate program, BCM, Houston, TX 77030, USA.
Marjorie WithersDepartment of Molecular and Human Genetics, BCM, Houston, TX 77030, USA.
Burak TepeDepartment of Molecular and Human Genetics, BCM, Houston, TX 77030, USA; Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Program in Developmental Biology, BCM, Houston, TX 77030, USA.
Benjamin R ArenkielDepartment of Molecular and Human Genetics, BCM, Houston, TX 77030, USA; Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Program in Developmental Biology, BCM, Houston, TX 77030, USA.
Priya S ShahDepartment of Chemical Engineering and Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA 95616, USA.
Nevan J KroganDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, QB3, University of California, San Francisco, San Francisco, CA 94158, USA.
Hatip AydinCenter of Genetics Diagnosis, Zeynep Kamil Maternity and Children's Training and Research Hospital, Istanbul, Turkey.
Bilgen B GeckinliDepartment of Medical Genetics, Marmara University School of Medicine, Istanbul, Turkey.
Tulay TosDepartment of Medical Genetics, Dr. Sami Ulus Research and Training Hospital of Women's and Children's Health and Diseases, Ankara, Turkey.
Sedat IsikayDepartment of Physiotherapy and Rehabilitation, Hasan Kalyoncu University, School of Health Sciences, Gaziantep, Turkey.
Beyhan TuysuzDepartment of Pediatrics, Istanbul University-Cerrahpasa, Medical Faculty, Istanbul, Turkey.
Ganesh H MochidaDivision of Genetics and Genomics, Department of Pediatrics and Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Pediatric Neurology Unit, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
Ajay X ThomasDepartment of Pediatrics, Section of Neurology and Developmental Neuroscience, BCM, Houston, TX 77030, USA; Section of Child Neurology, Texas Children's Hospital, Houston, TX 77030, USA.
Robin D ClarkDivision of Medical Genetics, Department of Pediatrics, Loma Linda University Medical Center, Loma Linda, CA 92354, USA.
Ghayda M MirzaaDepartment of Pediatrics, University of Washington, Seattle, WA 98195, USA; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98105, USA.
James R LupskiDepartment of Molecular and Human Genetics, BCM, Houston, TX 77030, USA; Department of Pediatrics, BCM, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Hugo J BellenHoward Hughes Medical Institute, BCM, Houston, TX 77030, USA; Department of Molecular and Human Genetics, BCM, Houston, TX 77030, USA; Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; MD/PhD Medical Scientist Training Program and MHG Graduate program, BCM, Houston, TX 77030, USA; Program in Developmental Biology, BCM, Houston, TX 77030, USA. Electronic address: hbellen@bcm.edu.
Baylor College of Medicine · USNeurological Research Institute · USTexas Children's Hospital · USBoston Children's Hospital · USHasan Kalyoncu University · TRHoward Hughes Medical Institute · USIstanbul University · TRLoma Linda University · USMarmara University · TRMinistry of Health · TRUniversity of California, Davis · USUniversity of California, San Francisco · USUniversity of Washington · USZeynep Kamil Hospital · TR

Funding

Transposon induced disruption of most Drosophila genesR01GM067858 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI BELLEN, HUGO J · 2003 to 2020
$15.7M
Baylor-Johns Hopkins Center for Mendelian GeneticsUM1HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2016 to 2020
$14.5M
Steps towards a paternal gene activation therapy for Angelman syndromeU54HD083092 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI NELSON, DAVID LOREN, SAMACO, RODNEY C · 2014 to 2019
$7.8M
Zebrafish CoreU54NS093793 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI BELLEN, HUGO J · 2015 to 2022
$7.5M
Expansion and characterization of the Drosophila Toolkit to study SARS-CoV-2R24OD022005 · OD · BAYLOR COLLEGE OF MEDICINE · PI BELLEN, HUGO J · 2016 to 2023
$7.4M
STRUCTURAL VARIATION IN NEUROLOGICAL DISEASER35NS105078 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI LUPSKI, JAMES R. · 2018 to 2025
$6.0M
R01 Application:Genetically Dissecting Cholinergic Signaling in Body Weight Control.R01DK109934 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI Benjamin R Arenkiel, Qingchun Tong · 2016 to 2026
$5.4M
MAPPING CONNECTIVITY ONTO POSTNATAL-BORN NEURONSR01NS078294 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI ARENKIEL, BENJAMIN R · 2012 to 2023
$3.6M
Genes and pathways underlying brain overgrowth and focal cortical malformationsK08NS092898 · NINDS · SEATTLE CHILDREN'S HOSPITAL · PI MIRZAA, GHAYDA · 2015 to 2019
$930k
Functional analysis of ANKLE2 in microcephaly using a genetic model systemF32NS092270 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI LINK, NICHOLE L · 2015 to 2017
$136k
Howard Hughes Medical InstituteNHGRI NIH HHS UM1 HG006542NICHD NIH HHS U54 HD083092NIDDK NIH HHS R01 DK109934NIGMS NIH HHS R01 GM067858NIH HHS R24 OD022005NINDS NIH HHS F32 NS092270NINDS NIH HHS K08 NS092898NINDS NIH HHS R01 NS078294NINDS NIH HHS R35 NS105078NINDS NIH HHS U54 NS093793
6 · The paper itself

Abstract

The apical Par complex, which contains atypical protein kinase C (aPKC), Bazooka (Par-3), and Par-6, is required for establishing polarity during asymmetric division of neuroblasts in Drosophila, and its activity depends on L(2)gl. We show that loss of Ankle2, a protein associated with microcephaly in humans and known to interact with Zika protein NS4A, reduces brain volume in flies and impacts the function of the Par complex. Reducing Ankle2 levels disrupts endoplasmic reticulum (ER) and nuclear envelope morphology, releasing the kinase Ballchen-VRK1 into the cytosol. These defects are associated with reduced phosphorylation of aPKC, disruption of Par-complex localization, and spindle alignment defects. Importantly, removal of one copy of ballchen or l(2)gl suppresses Ankle2 mutant phenotypes and restores viability and brain size. Human mutational studies implicate the above-mentioned genes in microcephaly and motor neuron disease. We suggest that NS4A, ANKLE2, VRK1, and LLGL1 define a pathway impinging on asymmetric determinants of neural stem cell division.

Indexed as

AnimalsAsymmetric Cell DivisionCell DivisionCell PolarityDrosophila melanogasterHumansMembrane ProteinsMicrocephalyMutationNeural Stem CellsNeuronsNuclear ProteinsZika VirusANKLE2 protein, humanMembrane ProteinsNuclear ProteinsaPKCBallchenBazookabrain developmentcongenital infectionL(2)glMCPH16MirandaNS4AVRK1

Identifiers

PMID31735666
PMCPMC6917859
OpenAlexW2989444414

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.