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<p>Recent studies have found non-immunological roles of the classical complement pathway (CP) in brain development and its involvement in neuropsychiatric and neurodegenerative diseases. However, multiple complement activation pathways exist beyond the CP, but their expression and function remain poorly understood in the brain. Using MERFISH, we constructed a comprehensive spatial transcriptomic atlas of the complement system in mouse brains from late embryonic stage to adulthood. Here we show that most complement genes are expressed locally with a remarkable degree of cellular, spatial, and temporal heterogeneity and that complement regulatory mechanisms are distinct from the periphery. Beyond confirming the known expression of the CP, our measurements reveal endogenous expression of the alternative pathway (AP), notably the AP activator Masp3 in immature brains. Masp3 deficiency alters molecular structure of the brain and causes working spatial memory defects, indicating a role of Masp3 in brain maturation, potentially via modulation of AP activity.</p>

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A spatial atlas of the complement system uncovers unique expression patterns in postnatal brain development in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月2日

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  • Yingying Zhang,
  • Brianna Watson,
  • Ajitanuj Rattan,
  • Tyrone Lee,
  • Smriti Chawla,
  • Ludwig Geistlinger,
  • Yilin Guan,
  • Finley B. Lord,
  • Minghe Ma,
  • Takashi Miwa,
  • Madhu Golla,
  • Barbara J. Caldarone,
  • Wen-chao Song,
  • Jeffrey R. Moffitt,
  • Michael C. Carroll

摘要

Recent studies have found non-immunological roles of the classical complement pathway (CP) in brain development and its involvement in neuropsychiatric and neurodegenerative diseases. However, multiple complement activation pathways exist beyond the CP, but their expression and function remain poorly understood in the brain. Using MERFISH, we constructed a comprehensive spatial transcriptomic atlas of the complement system in mouse brains from late embryonic stage to adulthood. Here we show that most complement genes are expressed locally with a remarkable degree of cellular, spatial, and temporal heterogeneity and that complement regulatory mechanisms are distinct from the periphery. Beyond confirming the known expression of the CP, our measurements reveal endogenous expression of the alternative pathway (AP), notably the AP activator Masp3 in immature brains. Masp3 deficiency alters molecular structure of the brain and causes working spatial memory defects, indicating a role of Masp3 in brain maturation, potentially via modulation of AP activity.