2. Academic Validation
  3. Vascular Lamb1 guides the migration of retinal microglial precursors via Itga6-Rac1 signaling

Vascular Lamb1 guides the migration of retinal microglial precursors via Itga6-Rac1 signaling

  • Cell Rep. 2025 Nov 25;44(11):116544. doi: 10.1016/j.celrep.2025.116544.
Dan Zhan 1,  Leyao Xu 1,  Wenjing Mu 1,  Binbin Jin 2,  Zhi Feng 2,  Shengnan Liu 1,  Chuan Wu 1,  Lingfei Luo 1,  Li Li 3
Affiliations

Affiliations

  • 1 Institute of Developmental Biology and Regenerative Medicine, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Southwest University, Chongqing 400715, China.
  • 2 Research Center of Stem Cells and Ageing, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, P.R. China.
  • 3 Research Center of Stem Cells and Ageing, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, P.R. China. Electronic address: [email protected].
PMID: 41206867 DOI: 10.1016/j.celrep.2025.116544
Abstract

Retinal microglia originate during embryonic hematopoiesis and play an essential role in visual function. However, the mechanisms guiding microglial precursors into the retina remain poorly understood. Here, we show that, in zebrafish embryos, microglial precursors enter the vitreous space via blood vessels, mainly the ventral radial vessel/hyaloid vein, before migrating to the developing retina. Vascular Lamb1 provides a haptotactic gradient sensed by Itga6 in microglial precursors, which activates Rac1 signaling to promote F-actin polarization and directional migration. Disruption of blood vessels or interference with the Lamb1-Itga6 axis blocks microglial precursor entry into the vitreous space and reduces retinal colonization. Similarly, LAMB1 is deposited in the blood vessels of mice, and endothelial-specific deficiency impairs microglial precursor settlement. These findings indicate a conserved Lamb1-Itga6 signaling axis that guides retinal microglial migration during development.

Keywords

CP: cell biology; CP: neuroscience; Itga6; Lamb1; blood vessel; microglial precursor; retina.

Figures
Products