Zebrafish Dpr2 inhibits mesoderm induction by promoting degradation of nodal receptors.
Nodal proteins, members of the transforming growth factor-beta (TGFbeta) superfamily, have been identified as key endogenous mesoderm inducers in vertebrates. Precise control of Nodal signaling is essential for normal development of embryos. Here, we report that zebrafish dapper2 (dpr2) is expressed in mesoderm precursors during early embryogenesis and is positively regulated by Nodal signals. In vivo functional studies in zebrafish suggest that Dpr2 suppresses mesoderm induction activities of Nodal signaling. Dpr2 is localized in late endosomes, binds to the TGFbeta receptors ALK5 and ALK4, and accelerates lysosomal degradation of these receptors.
Laboratory of Developmental Biology, Ministry of Education (MOE), Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
Lixia
L
Zhang
Hu
H
Zhou
Ying
Y
Su
Zhihui
Z
Sun
Haiwen
H
Zhang
Long
L
Zhang
Yu
Y
Zhang
Yuanheng
Y
Ning
Ye-Guang
YG
Chen
Anming
A
Meng
D030201:Activin Receptors, Type I / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism*; D004627:Embryonic Induction; D011992:Endosomes / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008247:Lysosomes / Q000378:metabolism; D008648:Mesoderm / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D055456:Nodal Signaling Ligands; D016376:Oligonucleotides, Antisense; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D055456:Nodal Signaling Ligands; D016376:Oligonucleotides, Antisense; D011506:Proteins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; C492594:dact2 protein, zebrafish; C485171:ndr1 protein, zebrafish; C512832:ndr2 protein, zebrafish; D017346:Protein Serine-Threonine Kinases; C425423:ACVR1 protein, human; C498932:ACVR1B protein, human; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human