RRC ID 80973
Author Goins LM, Girard JR, Mondal BC, Buran S, Su CC, Tang R, Biswas T, Kissi JA, Banerjee U.
Title Wnt signaling couples G2 phase control with differentiation during hematopoiesis in Drosophila.
Journal Dev Cell
Abstract During homeostasis, a critical balance is maintained between myeloid-like progenitors and their differentiated progeny, which function to mitigate stress and innate immune challenges. The molecular mechanisms that help achieve this balance are not fully understood. Using genetic dissection in Drosophila, we show that a Wnt6/EGFR-signaling network simultaneously controls progenitor growth, proliferation, and differentiation. Unlike G1-quiescence of stem cells, hematopoietic progenitors are blocked in G2 phase by a β-catenin-independent (Wnt/STOP) Wnt6 pathway that restricts Cdc25 nuclear entry and promotes cell growth. Canonical β-catenin-dependent Wnt6 signaling is spatially confined to mature progenitors through localized activation of the tyrosine kinases EGFR and Abelson kinase (Abl), which promote nuclear entry of β-catenin and facilitate exit from G2. This strategy combines transcription-dependent and -independent forms of both Wnt6 and EGFR pathways to create a direct link between cell-cycle control and differentiation. This unique combinatorial strategy employing conserved components may underlie homeostatic balance and stress response in mammalian hematopoiesis.
Published 2024-6-6
DOI 10.1016/j.devcel.2024.05.023
PII S1534-5807(24)00341-1
PMID 38866012
Drosophila 11561R-1