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Updated: Nov 26, 2025
Author Spotlight: Using Zebrafish to Explore Microglia Migration During Brain Development
Published on: May 17, 2024
A csf1rb mutation uncouples two waves of microglia development in zebrafish
Giuliano Ferrero1,2, Magali Miserocchi1,2, Elodie Di Ruggiero1
1Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Brussels 1070, Belgium.
Abstract:
In vertebrates, the ontogeny of microglia, the resident macrophages of the central nervous system, initiates early during development from primitive macrophages. Although murine embryonic microglia then persist through life, in zebrafish these cells are transient, as they are fully replaced by an adult population originating from larval hematopoietic stem cell (HSC)-derived progenitors. Colony-stimulating factor 1 receptor (Csf1r) is a fundamental regulator of microglia ontogeny in vertebrates, including zebrafish, which possess two paralogous genes: csf1ra and csf1rb Although previous work has shown that mutation in both genes completely abrogates microglia development, the specific contribution of each paralog remains largely unknown. Here, using a fate-mapping strategy to discriminate between the two microglial waves, we uncover non-overlapping roles for csf1ra and csf1rb in hematopoiesis, and identified csf1rb as an essential regulator of adult microglia development. Notably, we demonstrate that csf1rb positively regulates HSC-derived myelopoiesis, resulting in macrophage deficiency, including microglia, in adult mutant animals. Overall, this study contributes to new insights into evolutionary aspects of Csf1r signaling and provides an unprecedented framework for the functional dissection of embryonic versus adult microglia in vivo.
Insights
Zebrafish microglia are replaced during development. Colony-stimulating factor 1 receptor b (csf1rb) is crucial for adult microglia development by regulating hematopoietic stem cell (HSC)-derived myelopoiesis.
Area of Science:
- Developmental Biology
- Immunology
- Neuroscience
- Evolutionary Biology
Background:
- Microglia, the central nervous system's resident macrophages, originate from primitive macrophages during vertebrate development.
- In zebrafish, unlike mammals, microglia are transient and replaced by adult populations derived from hematopoietic stem cell (HSC) progenitors.
- Colony-stimulating factor 1 receptor (Csf1r) signaling is vital for microglia development, with zebrafish having two paralogs: csf1ra and csf1rb.
Purpose of the Study:
- To elucidate the distinct roles of csf1ra and csf1rb in zebrafish microglia ontogeny.
- To understand the specific contribution of each Csf1r paralog in regulating hematopoiesis and microglia development.
- To differentiate the developmental pathways of embryonic versus adult microglia in vivo.
Main Methods:
- Utilized a fate-mapping strategy to distinguish between embryonic and adult microglial populations.
- Investigated the effects of mutations in csf1ra and csf1rb on hematopoiesis and microglia development.
- Analyzed the regulation of HSC-derived myelopoiesis by csf1rb.
Main Results:
- Identified non-overlapping roles for csf1ra and csf1rb in hematopoiesis.
- Demonstrated that csf1rb is essential for adult microglia development.
- Showed that csf1rb positively regulates HSC-derived myelopoiesis, leading to macrophage and microglia deficiency in adult mutants.
Conclusions:
- csf1rb plays a critical role in the development of adult microglia by controlling HSC-derived myelopoiesis.
- This study reveals distinct functions for Csf1r paralogs in vertebrate hematopoiesis and microglia ontogeny.
- Provides a framework for studying embryonic vs. adult microglia development and Csf1r signaling evolution.
