Transcriptional factors smad1 and smad9 act redundantly to mediate zebrafish ventral specification downstream of smad5.
Bone morphogenetic proteins (BMPs) are multifunctional growth factors that play crucial roles during embryonic development and cell fate determination. Nuclear transduction of BMP signals requires the receptor type Smad proteins, Smad1, Smad5, and Smad9. However, how these Smad proteins cooperate in vivo to regulate various developmental processes is largely unknown. In zebrafish, it was widely believed that the maternally expressed smad5 is essential for dorso-ventral (DV) patterning, and the zygotically transcribed smad1 is not required for normal DV axis establishment. In the present study, we have identified zygotically expressed smad9, which cooperates with smad1 downstream of smad5, to mediate zebrafish early DV patterning in a functional redundant manner. Although knockdown of smad1 or smad9 alone does not lead to visible dorsalization, double knockdown strongly dorsalizes zebrafish embryos, which cannot be efficiently rescued by smad5 overexpression, whereas the dorsalization induced by smad5 knockdown can be fully rescued by overexpression of smad1 or smad9. We have further revealed that the transcription initiations of smad1 and smad9 are repressed by each other, that they are direct transcriptional targets of Smad5, and that smad9, like smad1, is required for myelopoiesis. In conclusion, our study uncovers that smad1 and smad9 act redundantly to each other downstream of smad5 to mediate ventral specification and to regulate embryonic myelopoiesis.
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Donghu South Road, Wuhan 430072, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
Chang-Yong
CY
Wei
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Donghu South Road, Wuhan 430072, China.
Hou-Peng
HP
Wang
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Donghu South Road, Wuhan 430072, China.
Zuo-Yan
ZY
Zhu
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Donghu South Road, Wuhan 430072, China. Electronic address: yhsun@ihb.ac.cn.
Yong-Hua
YH
Sun
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D008969:Molecular Sequence Data; D038042:Myelopoiesis / Q000235:genetics*; D010802:Phylogeny; D051898:Smad1 Protein / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D051902:Smad5 Protein / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D051904:Smad8 Protein / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D061785:Transcription Initiation, Genetic; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*
D019485:Bone Morphogenetic Proteins; D051898:Smad1 Protein; D051902:Smad5 Protein; D051904:Smad8 Protein; D029961:Zebrafish Proteins; C497801:smad5 protein, zebrafish
Bone Morphogenetic Protein (BMP); Development; Dorso-ventral Patterning; Gene Regulation; Myelopoiesis; SMAD Transcription Factor; Zebrafish