Lgr5 Marks Post-Mitotic, Lineage Restricted Cerebellar Granule Neurons during Postnatal Development.
Lgr5 Marks Post-Mitotic, Lineage Restricted Cerebellar Granule Neurons during Postnatal Development.
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LGR5标记有丝分裂后谱系限制的小脑颗粒神经元在产后发育过程中。
DOI：
10.1371/journal.pone.0114433
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Rich JN
中科院分区：
文献类型：
--
作者：
Miller TE;Wang J;Sukhdeo K;Horbinski C;Tesar PJ;Wechsler-Reya RJ;Rich JN
Wnt信号调节干细胞和祖细胞在发育和稳态中的自我更新和命运承诺。富含亮氨酸重复的G蛋白偶联受体5（Lgr 5）是Wnt信号传导的共受体，其在许多上皮组织类型中标记高度增殖的干细胞和祖细胞。Wnt信号指导神经发育和稳态过程;然而，Lgr 5在发育和成人大脑中的表达尚未被表征。在这里，我们报告说，LGR 5表达在出生后的小脑颗粒神经元（CGNs）的成熟和突触发生，Wnt信号控制的过程。使用转基因报告小鼠在体内Lgr 5表达分析和谱系追踪，我们发现，Lgr 5特异性识别CGNs，并在时间上限制在CGN成熟期内的内部颗粒层，但不存在于成年人的大脑。Lgr 5标记的细胞是谱系限制的，有丝分裂后和长寿命的。Lgr 5的配体R-spondin以旁分泌的方式分泌，该方式在CGN的成熟过程中演变，这与Lgr 5的表达模式相吻合。我们的研究结果提供了潜在的新的洞察力的关键调控Wnt信号在发育中的小脑和支持一个新的角色LGR 5在有丝分裂后的细胞的调节。
Wnt signaling regulates self-renewal and fate commitment of stem and progenitor cells in development and homeostasis. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is a co-receptor for Wnt signaling that marks highly proliferative stem and progenitor cells in many epithelial tissue types. Wnt signaling instructs neural developmental and homeostatic processes; however, Lgr5 expression in the developing and adult brain has not been characterized. Here we report that Lgr5 is expressed in the postnatal cerebellum during the maturation and synaptogenesis of cerebellar granule neurons (CGNs), processes controlled by Wnt signaling. Using a transgenic reporter mouse for in vivo Lgr5 expression analysis and lineage tracing, we reveal that Lgr5 specifically identified CGNs and was restricted temporally to the CGN maturation phase within the internal granule layer, but absent in the adult brain. Cells marked by Lgr5 were lineage restricted, post-mitotic and long-lived. The ligand for Lgr5, R-spondin, was secreted in a paracrine fashion that evolved during the maturation of CGNs, which coincided with the Lgr5 expression pattern. Our findings provide potential new insight into the critical regulation of Wnt signaling in the developing cerebellum and support a novel role for Lgr5 in the regulation of post-mitotic cells.
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影响因子：
6.2
作者：
Mulligan, Kimberly A.;Cheyette, Benjamin N. R.
通讯作者：
Cheyette, Benjamin N. R.
影响因子：
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作者：
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Schueller, Ulrich
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作者：
Barker, Nick;Tan, Shawna;Clevers, Hans
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Clevers, Hans
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Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
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Zeng H
影响因子：
16.2
作者：
Wechsler-Reya, RJ;Scott, MP
通讯作者：
Scott, MP