Department of Genetics, College of Life Sciences, Northeast Forestry University, Harbin 150040, China.
Department of Basic Medical, Shenyang Medical College, Shenyang 110034, China.
Cells. 2023 Feb 19;12(4):661. 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.
淋巴腺是研究造血的理想模型，阐明造血的机制可以提高我们对人类造血恶性肿瘤发病机制的理解。骨形态发生蛋白 (BMP) 信号转导参与多种生物学过程，在 和哺乳动物之间高度保守。已知颅顶发育不全 (Dpp)/BMP 信号通过抑制原癌基因 来限制后信号中心 (PSC) 细胞的增殖。然而，两种其他 TGF-β家族配体 Glass bottom boat (Gbb) 和 Screw (Scw) 在 造血中的作用目前在很大程度上是未知的。在这里，我们表明 Gbb 在皮质区 (CZ) 的缺失通过过度激活 EGFR 和 JNK 途径诱导 lamellocyte 分化，并导致浆细胞的过度分化，主要是通过 EGFR 的过度激活。此外，我们发现 Gbb 还通过抑制表皮生长因子受体 (EGFR) 和 c-Jun N-末端激酶 (JNK) 途径的过度激活来防止淋巴腺的过度增殖。这些结果进一步提高了我们对 Gbb 蛋白和 BMP 信号在 造血中的作用以及 BMP、EGFR 和 JNK 途径在淋巴腺血细胞增殖和分化中的调控关系的理解。
