TY - JOUR
T1 - Erratic and blood vessel-guided migration of astrocyte progenitors in the cerebral cortex
AU - Tabata, Hidenori
AU - Sasaki, Megumi
AU - Agetsuma, Masakazu
AU - Sano, Hitomi
AU - Hirota, Yuki
AU - Miyajima, Michio
AU - Hayashi, Kanehiro
AU - Honda, Takao
AU - Nishikawa, Masashi
AU - Inaguma, Yutaka
AU - Ito, Hidenori
AU - Takebayashi, Hirohide
AU - Ema, Masatsugu
AU - Ikenaka, Kazuhiro
AU - Nabekura, Junichi
AU - Nagata, Koh ichi
AU - Nakajima, Kazunori
N1 - Funding Information:
We are grateful to C.G.Lobe for Z/EG mice, K. Kawakami and Y. Takahashi for pCAGGS-T2TP and pT2K-CAGGS-mCherry, A. Miyawaki for kikGR cDNA, J. Miyazaki for CAG promoter, U. Lendahl for nestin promoter, C. Cepko for pCALNL-DsRed, S. Miyagawa for codon usage-optimized Cre, Y. Mizutani and K. Yoshizaki for manipulation of Flt1-DsRed mouse embryos, Y. Gotoh and K. Nakashima for their help to breed the Aldh1l1-GFP mice, N. Hane, T. Nagano, I. Iwamoto and H. Arai for technical supports, and M. Yoshitomo and T. Kobayashi for their assistance in preparing two-photon imaging. We also thank N. Hiroi for technical supports in single cell RNA-seq data analysis. This work was supported by JSPS KAKENHI [Grant Number JP21K07309 to H.Tabata, JP20H05688, JP16H06482, and JP22K19365 to K.Nakajima, JP16H06280 (Platforms for Advanced Technologies and Research Resources “Advanced Bioimaging Support”) to M.A. and J.N., JP21K06413, and JP18K06508 to T.H.], Takeda Science Foundation, Keio Gijuku Academic Development Funds, and Keio Gijuku Fukuzawa Memorial Fund to K.Nakajima.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Astrocytes are one of the most abundant cell types in the mammalian brain. They play essential roles in synapse formation, maturation, and elimination. However, how astrocytes migrate into the gray matter to accomplish these processes is poorly understood. Here, we show that, by combinational analyses of in vitro and in vivo time-lapse observations and lineage traces, astrocyte progenitors move rapidly and irregularly within the developing cortex, which we call erratic migration. Astrocyte progenitors also adopt blood vessel-guided migration. These highly motile progenitors are generated in the restricted prenatal stages and differentiate into protoplasmic astrocytes in the gray matter, whereas postnatally generated progenitors do not move extensively and differentiate into fibrous astrocytes in the white matter. We found Cxcr4/7, and integrin β1 regulate the blood vessel-guided migration, and their functional blocking disrupts their positioning. This study provides insight into astrocyte development and may contribute to understanding the pathogenesis caused by their defects.
AB - Astrocytes are one of the most abundant cell types in the mammalian brain. They play essential roles in synapse formation, maturation, and elimination. However, how astrocytes migrate into the gray matter to accomplish these processes is poorly understood. Here, we show that, by combinational analyses of in vitro and in vivo time-lapse observations and lineage traces, astrocyte progenitors move rapidly and irregularly within the developing cortex, which we call erratic migration. Astrocyte progenitors also adopt blood vessel-guided migration. These highly motile progenitors are generated in the restricted prenatal stages and differentiate into protoplasmic astrocytes in the gray matter, whereas postnatally generated progenitors do not move extensively and differentiate into fibrous astrocytes in the white matter. We found Cxcr4/7, and integrin β1 regulate the blood vessel-guided migration, and their functional blocking disrupts their positioning. This study provides insight into astrocyte development and may contribute to understanding the pathogenesis caused by their defects.
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U2 - 10.1038/s41467-022-34184-x
DO - 10.1038/s41467-022-34184-x
M3 - Article
C2 - 36323680
AN - SCOPUS:85141171357
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 6571
ER -