PT  - JOURNAL ARTICLE
AU  - Shoutang Wang
AU  - Deshan Ren
AU  - Anna-Lila Kaushik
AU  - Gabriel Matherat
AU  - Yann Lécluse
AU  - Dominik Filipp
AU  - William Vainchenker
AU  - Hana Raslova
AU  - Isabelle Plo
AU  - Isabelle Godin
TI  - Lyl-1 marks and regulates primitive macrophages and microglia development
AID  - 10.1101/2020.09.28.316570
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.28.316570
4099  - http://biorxiv.org/content/early/2020/09/28/2020.09.28.316570.short
4100  - http://biorxiv.org/content/early/2020/09/28/2020.09.28.316570.full
AB  - During ontogeny, resident macrophages (MΦs) of the nervous system emerge from haematopoietic stem cell-independent progenitors originating in the Yolk Sac (YS), so that factors impairing YS MΦ development may lead to neurodevelopmental disorders resulting from defective brain resident MΦ.Here we show that Lyl-1, a bHLH transcription factor related to Scl/Tal-1, marks primitive macrophage (MΦPrim) progenitors in the YS. Transcriptomic analysis of YS MΦ progenitors indicated that MΦPrim progenitors present at embryonic day (E) 9 are clearly distinct from those present at E10. Lyl-1 bHLH disruption led to an increased production and a defective differentiation of MΦPrim progenitors. These differentiation defects were associated with profound modifications of the expression of genes involved in embryonic patterning and neurodevelopment. They also induced a reduced production of mature MΦ/microglia in the early brain, as well as a transient reduction of the microglia pool at midgestation and in the new-born.We thus identify Lyl-1 as a critical regulator of MΦPrim and microglia development, which disruption may impair organogenesis, including neurodevelopment processes.Key pointsLyl-1 expression marks yolk sac macrophages and brain macrophage/microglia/BAM.Lyl-1 deficiency impairs primitive macrophage development and leads to the up-regulation of genes involved in embryo patterning.Lyl-1-expressing primitive macrophages have an immuno-modulatory phenotype.Lyl-1 deficiency impairs microglia development and the expression of genes involved in neuro-development.Competing Interest StatementThe authors have declared no competing interest.