Embryonic microglia derive from primitive macrophages and are replaced by cmyb-dependent definitive microglia in zebrafish
Giuliano
Ferrero1, 2*,
Chris
Mahony3, 4,
Eleonore
Dupuis1, 2,
Laurent
Yvernogeau5,
Elodie
Di Ruggiero1, 2,
Magali
Miserocchi1, 2,
Marianne
Caron1,
Catherine
Robin5,
David
Traver6,
Julien
Y.
BERTRAND4 and
Valerie
Wittamer1, 2*
-
1
Free University of Brussels, Belgium
-
2
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Belgium
-
3
Université de Genève, Switzerland
-
4
Department of Pathology and Immunology, University of Geneva, Switzerland
-
5
Hubrecht Institute (KNAW), Netherlands
-
6
Departments of Medicine and Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, United States
With no current cure and an increasing prevalence in our ageing society, neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases represent a burden to industrialized countries. Because these diseases are often associated with neuroinflammation, microglia, the resident macrophages in the central nervous system, represent a potential target for the development of novel therapeutic approaches. Our current understanding of microglia ontogeny suggests that maintenance and expansion of steady-state microglia are strictly dependent on self-renewing local progenitors that seed the brain early during embryogenesis. Although several candidates have been suggested, the identity of these local progenitors is currently a controversial topic and remained to be determined. Utilizing the unique attributes of the zebrafish embryo, we have investigated the cellular and molecular mechanisms underlying microglia ontogeny in vertebrates. Here, we show that microglia arise in two independent waves during zebrafish development. First, primitive macrophages generate a transient wave of embryonic microglia. This primitive wave is replaced by definitive microglia that persist throughout adulthood. Fate-mapping analyses revealed that the second wave of microglia derives from Hematopoietic Stem Cells (HSCs), that are specified early during embryogenesis. A thorough dissection of the molecular pathways that specifically instruct adult and embryonic microglia ontogeny may significantly contribute to the generation of bona-fide microglia cells from hematopoietic progenitors in-vivo and in-vitro, a goal that is largely unmet so far.
Keywords:
Microglia,
hematopoieisis,
development,
Zebrafish,
lineage-tracing
Conference:
13th National Congress of the Belgian Society for Neuroscience , Brussels, Belgium, 24 May - 24 May, 2019.
Presentation Type:
Poster presentation
Topic:
Cellular/Molecular Neuroscience
Citation:
Ferrero
G,
Mahony
C,
Dupuis
E,
Yvernogeau
L,
Di Ruggiero
E,
Miserocchi
M,
Caron
M,
Robin
C,
Traver
D,
BERTRAND
JY and
Wittamer
V
(2019). Embryonic microglia derive from primitive macrophages and are replaced by cmyb-dependent definitive microglia in zebrafish.
Front. Neurosci.
Conference Abstract:
13th National Congress of the Belgian Society for Neuroscience .
doi: 10.3389/conf.fnins.2019.96.00078
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Received:
15 Apr 2019;
Published Online:
27 Sep 2019.
*
Correspondence:
Mr. Giuliano Ferrero, Free University of Brussels, Brussels, Brussels, 1050, Belgium, ferrero.giuliano@gmail.com
Mx. Valerie Wittamer, Free University of Brussels, Brussels, Brussels, 1050, Belgium, vwittame@ulb.ac.be