Cited by 54Neurogenesis and neuroplasticity mechanismsGenomic variations and chromosomal abnormalitiesFetal and Pediatric Neurological Disorders

Ranbp1 , Deleted in DiGeorge/22q11.2 Deletion Syndrome, is a Microcephaly Gene That Selectively Disrupts Layer 2/3 Cortical Projection Neuron Generation

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Paronett, Elizabeth M., Meechan, Daniel W., Karpinski, Beverly A., LaMantia, Anthony-Samuel, Maynard, Thomas M.·2015·Cerebral Cortex

Abstract

Ranbp1, a Ran GTPase-binding protein implicated in nuclear/cytoplasmic trafficking, is included within the DiGeorge/22q11.2 Deletion Syndrome (22q11.2 DS) critical region associated with behavioral impairments including autism and schizophrenia. Ranbp1 is highly expressed in the developing forebrain ventricular/subventricular zone but has no known obligate function during brain development. We assessed the role of Ranbp1 in a targeted mouse mutant. Ranbp1(-/-) mice are not recovered live at birth, and over 60% of Ranbp1(-/-) embryos are exencephalic. Non-exencephalic Ranbp1(-/-) embryos are microcephalic, and proliferation of cortical progenitors is altered. At E10.5, radial progenitors divide more slowly in the Ranpb1(-/-) dorsal pallium. At E14.5, basal, but not apical/radial glial progenitors, are compromised in the cortex. In both E10.5 apical and E14.5 basal progenitors, M phase of the cell cycle appears selectively retarded by loss of Ranpb1 function. Ranbp1(-/-)-dependent proliferative deficits substantially diminish the frequency of layer 2/3, but not layer 5/6 cortical projection neurons. Ranbp1(-/-) cortical phenotypes parallel less severe alterations in LgDel mice that carry a deletion parallel to many (but not all) 22q11.2 DS patients. Thus, Ranbp1 emerges as a microcephaly gene within the 22q11.2 deleted region that may contribute to altered cortical precursor proliferation and neurogenesis associated with broader 22q11.2 deletion.

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  • Ranbp1−/− embryos show reduced proliferation of basal progenitor cells, leading to fewer layer II and III projection neurons.

    “and reduced proliferation of basal progenitor cells, leading to fewer layer II and III projection neurons in Ranbp1−/− embryos [274].”

    From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [274]

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Authors
Paronett, E. M., Meechan, D. W., Karpinski, B. A., LaMantia, A.-S., & Maynard, T. M.
Affiliations
George Washington University (US)
Corresponding author
Paronett, Elizabeth M.
Venue
Cerebral Cortex
Published
2014-12-01
Volume
25
Issue
10
Pages
3977-3993
ISSN
  • 1047-3211 (ISSN-L)
  • 1460-2199
OpenAlex
W2031405257
Cited by
54
References
87
Citations by year
2026: 5 · 2025: 4 · 2024: 1 · 2023: 8 · 2022: 7 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 6 · 2016: 2 · 2015: 4
FWCI
1.39
Type
journal article
Language
en
Open access
Locations
  • Cerebral Cortex (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Child Health and Human Development (HD042182)
  • National Center for Research Resources (S10RR025565)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD40677, P30HD040677, P01HD083157, R01HD042182, HD042182)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
Keywords
RanBP1, 22q11.2 deletion syndrome, microcephaly, cortical projection neurons, layer 2/3 neurons, radial glial progenitors, basal progenitors, exencephaly, Ran GTPase, nuclear-cytoplasmic trafficking, neurogenesis, autism spectrum disorder, schizophrenia
MeSH terms
Animals, Cerebral Cortex, DiGeorge Syndrome, Mice, Inbred C57BL, Microcephaly, Nuclear Proteins, Cell Polarity, Mice, Knockout, Lateral Ventricles, Neuroepithelial Cells, Cell Proliferation, Mice, Neurogenesis, Neural Stem Cells

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