The zinc finger transcription factor Sall1 is required for the early developmental transition of microglia in mouse embryos.
The zinc finger transcription factor Sall1 is required for the early developmental transition of microglia in mouse embryos.
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DOI：
10.1002/glia.24192
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发表时间：
2022-09
期刊：
影响因子：
6.2
通讯作者：
Nakagawa, Yasushi
中科院分区：
文献类型：
--
作者：
Scott, Earl Parker;Breyak, Emma;Nishinakamura, Ryuichi;Nakagawa, Yasushi
小胶质细胞在神经发育中发挥着许多关键作用。最近的单细胞RNA测序研究发现，在发育中的大脑中，不同阶段和同一阶段的小胶质细胞都具有多样性。然而，在发育过程中如何控制这种多样性却知之甚少。在这项研究中，我们首次发现巨噬细胞甘露糖受体CD206在小鼠脑切片上的早期胚胎小胶质细胞中表达。这种表达在整个中枢神经系统中显示出E12.5和E13.5之间的急剧下降。接下来，我们测试了小胶质细胞表达的锌指转录因子SALL1在基因表达早期转换中的作用。通过在小胶质细胞中特异性地删除Sall1，我们发现许多小胶质细胞在正常下调时继续表达CD206。此外，突变的小胶质细胞继续表现出较少的分枝形态与对照组相比，甚至到出生后阶段。因此，SALL1是早期小胶质细胞在发育过程中过渡到更成熟状态所必需的。锌指转录因子Sall1是小鼠胚胎脑发育过程中早期小胶质细胞向成熟类型转化所必需的。
Microglia play many critical roles in neural development. Recent single‐cell RNA‐sequencing studies have found diversity of microglia both across different stages and within the same stage in the developing brain. However, how such diversity is controlled during development is poorly understood. In this study, we first found the expression of the macrophage mannose receptor CD206 in early‐stage embryonic microglia on mouse brain sections. This expression showed a sharp decline between E12.5 and E13.5 across the central nervous system. We next tested the roles of the microglia‐expressed zinc finger transcription factor SALL1 in this early transition of gene expression. By deleting Sall1 specifically in microglia, we found that many microglia continued to express CD206 when it is normally downregulated. In addition, the mutant microglia continued to show less ramified morphology in comparison with controls even into postnatal stages. Thus, SALL1 is required for early microglia to transition into a more mature status during development. Zinc finger transcription factor Sall1 is required for the transition of early microglia to a more mature types during embryonic mouse brain development.
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