Subcellular mRNA localization and local translation of Arhgap11a in radial glial progenitors regulates cortical development

被引:10
|
作者
Pilaz, Louis-Jan [1 ,2 ,3 ]
Liu, Jing [1 ]
Joshi, Kaumudi [4 ]
Tsunekawa, Yuji [5 ]
Musso, Camila M. [1 ]
D'Arcy, Brooke R. [1 ]
Suzuki, Ikuo K. [6 ]
Alsina, Fernando C. [1 ]
Pratiksha, K. C. [2 ,3 ]
Sethi, Sahil [1 ]
Vanderhaeghen, Pierre [7 ,8 ,9 ,10 ,11 ]
Polleux, Franck [4 ,12 ,13 ]
Silver, Debra L. [1 ,14 ,15 ,16 ,17 ]
机构
[1] Duke Univ, Sch Med, Dept Mol Genet & Microbiol, Durham, NC 27710 USA
[2] Sanford Res, Pediat & Rare Dis Grp, Sioux Falls, SD 57104 USA
[3] Univ South Dakota, Sanford Sch Med, Dept Pediat, Sioux Falls, SD 57105 USA
[4] Columbia Univ, Med Ctr, Dept Neurosci, New York, NY 10032 USA
[5] RIKEN Ctr Biosyst Dynam Res, Lab Cell Asymmetry, Kobe, Hyogo, Japan
[6] Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Tokyo, Japan
[7] VIB KU Leuven, Ctr Brain & Dis Res, B-3000 Louvain, Belgium
[8] Katholieke Univ Leuven, Dept Neurosci, B-3000 Leuven, Belgium
[9] Leuven Brain Inst, B-3000 Leuven, Belgium
[10] Univ Libre Bruxelles ULB, Inst Rech Biol Humaine & Mol IRIBHM, B-1070 Brussels, Belgium
[11] ULB Neurosci Inst UNI, B-1070 Brussels, Belgium
[12] Mortimer B Zuckerman Mind Brain Behav Inst, New York, NY 10027 USA
[13] Columbia Univ, Med Ctr, Kavli Inst Brain Sci, New York, NY 10027 USA
[14] Duke Univ, Sch Med, Dept Cell Biol, Durham, NC 27710 USA
[15] Duke Univ, Sch Med, Dept Neurobiol, Durham, NC 27710 USA
[16] Duke Univ, Sch Med, Duke Inst Brain Sci, Durham, NC 27710 USA
[17] Duke Univ, Sch Med, Duke Regenerat Ctr, Durham, NC 27710 USA
关键词
OUTER SUBVENTRICULAR ZONE; MOUSE-BRAIN; CYCLIN D2; CELLS; NEURONS; DIVERSITY; MIGRATION; LAYERS; PROLIFERATION; SPECIFICATION;
D O I
10.1016/j.neuron.2023.02.023
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
mRNA localization and local translation enable exquisite spatial and temporal control of gene expression, particularly in polarized, elongated cells. These features are especially prominent in radial glial cells (RGCs), which are neural and glial precursors of the developing cerebral cortex and scaffolds for migrating neurons. Yet the mechanisms by which subcellular RGC compartments accomplish their diverse functions are poorly understood. Here, we demonstrate that mRNA localization and local translation of the RhoGAP ARHGAP11A in the basal endfeet of RGCs control their morphology and mediate neuronal positioning. Arh-gap11a transcript and protein exhibit conserved localization to RGC basal structures in mice and humans, conferred by the 50 UTR. Proper RGC morphology relies upon active Arhgap11a mRNA transport and local-ization to the basal endfeet, where ARHGAP11A is locally synthesized. This translation is essential for posi-tioning interneurons at the basement membrane. Thus, local translation spatially and acutely activates Rho signaling in RGCs to compartmentalize neural progenitor functions.
引用
收藏
页码:839 / +
页数:24
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