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

Dan Zhan1, Leyao Xu1, Wenjing Mu1

  • 1Institute of Developmental Biology and Regenerative Medicine, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Southwest University, Chongqing 400715, China.

Cell Reports
|November 9, 2025
PubMed

Insights

Retinal microglia precursors migrate via blood vessels, guided by vascular Lamb1 interacting with Itga6. This conserved signaling pathway is crucial for their entry into the eye and colonization of the retina during development.

Area of Science:

  • Developmental biology
  • Neuroscience
  • Ophthalmology

Background:

  • Microglia are essential for visual function, originating from embryonic hematopoiesis.
  • The precise mechanisms guiding microglial precursors to the retina are not fully understood.

Purpose of the Study:

  • To elucidate the mechanisms of microglial precursor migration into the developing retina.
  • To identify key molecular interactions guiding this process.

Main Methods:

  • Zebrafish and mouse models were used to study microglial precursor migration.
  • Genetic manipulation and imaging techniques were employed to analyze vascular guidance cues and cell migration.

Main Results:

  • Microglial precursors enter the vitreous space via blood vessels, primarily the hyaloid vein.
  • Vascular Laminin beta 1 (Lamb1) acts as a haptotactic cue, binding to Integrin alpha 6 (Itga6) on precursors.
  • This interaction activates Rac1 signaling, promoting directional migration and retinal colonization.
  • Disruption of the Lamb1-Itga6 axis or blood vessels impairs microglial entry and settlement.

Conclusions:

  • A conserved Lamb1-Itga6 signaling axis guides retinal microglial precursor migration during development.
  • Blood vessels play a critical role in delivering microglial precursors to the retina.