Jingyun Li1, Kui Li, Xiaohua Dong, Dong Liang, Qingshun Zhao. 1. MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China; Maternal and Child Health Medical Institute, Nanjing Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Abstract
BACKGROUND: Although Ncor1 and Ncor2, the co-repressors that can actively repress gene transcription through binding nuclear receptors in the absence of ligands, are crucial to vertebrate embryogenesis, their roles in its primitive myelopoiesis remain unknown. We investigated the function of ncor1 or ncor2 in zebrafish embryos by antisense morpholino knocking down technologies. RESULTS: Development of both mfap4(+) macrophages and mpx(+) neutrophils was abolished in ncor2 morphants, whereas development of mpx(+) neutrophils was depleted in ncor1 morphants. ncor2 was essential to the development of spi1b(+) myeloid precursors but not anterior hemangioblasts whereas ncor1 was dispensable to the specification of spi1b(+) myeloid precursors and anterior hemangioblasts. Overexpressing spi1b could partially rescue expressions of mfap4 and mpx in ncor2 morphants. Furthermore, overexpressing tal1/lmo2 could well rescue the defective myelopoiesis in both ncor1 and ncor2 morphants. CONCLUSIONS: Ncor1 and Ncor2 play essential but distinct roles in zebrafish primitive myelopoiesis. ncor2 could parallel with tal1/lmo2 and acted upstream of spi1b to produce mature macrophages and neutrophils during primitive myelopoiesis. The role of ncor1 in zebrafish myelopoiesis could be substituted by excessive Tal1/Lmo2.
BACKGROUND: Although Ncor1 and Ncor2, the co-repressors that can actively repress gene transcription through binding nuclear receptors in the absence of ligands, are crucial to vertebrate embryogenesis, their roles in its primitive myelopoiesis remain unknown. We investigated the function of ncor1 or ncor2 in zebrafish embryos by antisense morpholino knocking down technologies. RESULTS: Development of both mfap4(+) macrophages and mpx(+) neutrophils was abolished in ncor2 morphants, whereas development of mpx(+) neutrophils was depleted in ncor1 morphants. ncor2 was essential to the development of spi1b(+) myeloid precursors but not anterior hemangioblasts whereas ncor1 was dispensable to the specification of spi1b(+) myeloid precursors and anterior hemangioblasts. Overexpressing spi1b could partially rescue expressions of mfap4 and mpx in ncor2 morphants. Furthermore, overexpressing tal1/lmo2 could well rescue the defective myelopoiesis in both ncor1 and ncor2 morphants. CONCLUSIONS:Ncor1 and Ncor2 play essential but distinct roles in zebrafish primitive myelopoiesis. ncor2 could parallel with tal1/lmo2 and acted upstream of spi1b to produce mature macrophages and neutrophils during primitive myelopoiesis. The role of ncor1 in zebrafish myelopoiesis could be substituted by excessive Tal1/Lmo2.