ZFIN ID: ZDB-PUB-161011-12
BLOS2 negatively regulates Notch signaling during neural and hematopoietic stem and progenitor cell development
Zhou, W., He, Q., Zhang, C., He, X., Cui, Z., Liu, F., Li, W.
Date: 2016
Source: eLIFE 5: (Journal)
Registered Authors: Cui, Zongbin, Liu, Feng, Zhang, Chunxia
Keywords: cell biology, developmental biology, mouse, stem cells, zebrafish
MeSH Terms: Animals; Cell Differentiation*; Cell Proliferation*; Hematopoietic Stem Cells/physiology*; Mice, Inbred C57BL/embryology (all 11) expand
PubMed: 27719760 Full text @ Elife
FIGURES   (current status)
ABSTRACT
Notch signaling plays a crucial role in the control of proliferation and differentiation of stem and progenitor cells during embryogenesis or organogenesis, but its regulation is incompletely understood. BLOS2, encoded by the Bloc1s2 gene, is a shared subunit of two lysosomal trafficking complexes, biogenesis of lysosome-related organelles complex-1 (BLOC-1) and BLOC-1 related complex. Bloc1s2(-/-) mice were embryonic lethal and exhibited defects in cortical development and hematopoiesis. Loss of BLOS2 resulted in elevated Notch signaling, which consequently increased the proliferation of neural progenitor cells and inhibited neuronal differentiation in cortices. Likewise, ablation of bloc1s2 in zebrafish or mice led to increased hematopoietic stem and progenitor cell production in the aorta-gonad-mesonephros region. BLOS2 physically interacted with Notch1 in endo-lysosomal trafficking of Notch1. Our findings suggest that BLOS2 is a novel negative player in regulating Notch signaling through lysosomal trafficking by controlling multiple stem and progenitor cell homeostasis in vertebrates.
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