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

• Published in: Cells (Basel, Switzerland) Switzerland), 2023-02, Vol.12 (4), p.661
• Main Authors: Zhang, Wenhao, Wang, Dongmei, Si, Jingjing, Jin, Li Hua, Hao, Yangguang
• Format: Article
• Language: English
• Subjects: Animals; Blood; Bone morphogenetic proteins; c-Jun protein; Cell differentiation; Cell growth; Cell Proliferation; Drosophila; Drosophila - metabolism; Drosophila Proteins - metabolism; EGFR; Epidermal growth factor receptors; ErbB Receptors - metabolism; Experiments; Gbb; Gbb protein; Hematopoiesis; Hemocytes; Hemopoiesis; Humans; Insects; JNK; JNK protein; Kinases; Leukemia; Ligands; Lymph; Lymph gland; Malignancy; Mammals - metabolism; Plasmatocytes; Proteins; Receptors, Invertebrate Peptide; Signal transduction; Signal Transduction - physiology; Stem cells; Transcription factors; Transforming growth factor-b
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12040661

The lymph gland is an ideal model for studying hematopoiesis, and unraveling the mechanisms of 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 and mammals. Decapentaplegic (Dpp)/BMP signaling is known to limit posterior signaling center (PSC) cell proliferation by repressing the protooncogene . However, the role of two other TGF-β family ligands, Glass bottom boat (Gbb) and Screw (Scw), in 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 hematopoiesis and the regulatory relationship between the BMP, EGFR, and JNK pathways in the proliferation and differentiation of lymph gland hemocytes.