Gbb Regulates Blood Cell Proliferation and Differentiation through JNK and EGFR Signaling Pathways in the Drosophila Lymph Gland

Cells. 2023 Feb 19;12(4):661. doi: 10.3390/cells12040661.

Abstract

The Drosophila lymph gland is an ideal model for studying hematopoiesis, and unraveling the mechanisms of Drosophila hematopoiesis can improve our understanding of the pathogenesis of human hematopoietic malignancies. Bone morphogenetic protein (BMP) signaling is involved in a variety of biological processes and is highly conserved between Drosophila and mammals. Decapentaplegic (Dpp)/BMP signaling is known to limit posterior signaling center (PSC) cell proliferation by repressing the protooncogene dmyc. However, the role of two other TGF-β family ligands, Glass bottom boat (Gbb) and Screw (Scw), in Drosophila hematopoiesis is currently largely unknown. Here, we showed that the loss of Gbb in the cortical zone (CZ) induced lamellocyte differentiation by overactivation of the EGFR and JNK pathways and caused excessive differentiation of plasmatocytes, mainly by the hyperactivation of EGFR. Furthermore, we found that Gbb was also required for preventing the hyperproliferation of the lymph glands by inhibiting the overactivation of the Epidermal Growth Factor Receptor (EGFR) and c-Jun N-terminal Kinase (JNK) pathways. These results further advance our understanding of the roles of Gbb protein and the BMP signaling in Drosophila hematopoiesis and the regulatory relationship between the BMP, EGFR, and JNK pathways in the proliferation and differentiation of lymph gland hemocytes.

Keywords: EGFR; Gbb; JNK; hematopoiesis; lymph gland.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Drosophila Proteins* / metabolism
  • Drosophila* / metabolism
  • ErbB Receptors / metabolism
  • Hematopoiesis
  • Humans
  • Mammals / metabolism
  • Receptors, Invertebrate Peptide
  • Signal Transduction / physiology

Substances

  • Drosophila Proteins
  • ErbB Receptors
  • EGFR protein, human
  • dpp protein, Drosophila
  • Egfr protein, Drosophila
  • Receptors, Invertebrate Peptide

Grants and funding

This work was supported by the National Natural Science Foundation of China (31900366 to Y.H.) and the Shenyang Medical College of Science and Technology fund project (20186064 to Y.H.).