Maternal Activin-like proteins, a subgroup of the TGF-beta superfamily, play a key role in establishing the body axes in many vertebrates, but their role in teleosts is unclear. At least two maternal Activin-like proteins are expressed in zebrafish, including the Vg1 orthologue, zDVR-1, and the nodal-related gene, Squint. Our analysis of embryos lacking both maternal and zygotic squint function revealed that maternal squint is required in some genetic backgrounds for the formation of dorsal and anterior tissues. Conditional inactivation of the ALK4, 5 and 7 receptors by SB-505124 treatment during the cleavage stages ruled out a role for maternal Squint, zDVR-1, or other Activin-like ligands before the mid-blastula transition, when the dorsal axis is established. Furthermore, we show that maternal Squint and zDVR-1 are not required during the cleavage stages to induce zygotic nodal-related gene expression. nodal-related gene expression decreases when receptor inhibition continues past the mid-blastula transition, resulting in a progressive loss of mesoderm and endoderm. We conclude that maternally expressed Activin-like signals do not act before the mid-blastula transition in zebrafish, but do have a variably penetrant role in the later stages of axis formation. This contrasts with the early role for these signals during Xenopus development.
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http://dx.doi.org/10.1016/j.ydbio.2007.07.010 | DOI Listing |
Curr Res Pharmacol Drug Discov
July 2022
Case Comprehensive Cancer Center Research Laboratories, The Division of General Medical Sciences-Oncology Case Western Reserve University, Cleveland, OH, 44106, USA.
The mammalian target of rapamycin (mTOR) plays an important role in the aggressiveness and therapeutic resistance of many cancers. Targeting mTOR continues to be under clinical investigation for cancer therapy. Despite the notable clinical success of mTOR inhibitors in extending the overall survival of patients with certain malignancies including metastatic renal cell carcinomas (RCCs), the overall impact of mTOR inhibitors on cancers has been generally disappointing and attributed to various compensatory responses.
View Article and Find Full Text PDFInt J Dev Biol
May 2022
Department of Fisheries, Faculty of Natural Resources, University of Tehran, Karaj, Iran.
To investigate the role of maternal Activin-like factors in the preservation of stemness and mesendoderm induction, their effects were promoted and inhibited using synthetic human Activin A or SB-505124 treatments, respectively, before the maternal to zygotic transition (MZT). To study the role of zygotic Activin-like factors, SB-505124 treatment was also used after the MZT. Promoting the signaling intensity of maternal Activin-like factors led to premature differentiation, loss of stemness, and no mesendoderm malformation, while its alleviation delayed the differentiation and caused various malformations.
View Article and Find Full Text PDFJ Exp Zool B Mol Dev Evol
November 2021
Department of Radiology, Isfahan University of Medical Sciences, Isfahan, Iran.
Activin-like factors control many developmental processes, including pluripotency maintenance and differentiation. Although Activin-like factors' action in mesendoderm induction has been demonstrated in zebrafish, their involvement in preserving the stemness remains unknown. To investigate the role of maternal Activin-like factors, their effects were promoted or blocked using synthetic human Activin A or SB-431542 treatments respectively until the maternal to zygotic transition.
View Article and Find Full Text PDFMol Med Rep
January 2018
Department of Orthopedics, Tangdu Hospital of The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
Osteoarthritis (OA) is a common degenerative joint disease; however, its underlying pathogenesis remains to be elucidated. Previous studies have demonstrated that the transforming growth factor‑β (TGF‑β) signaling pathway has a role in the initiation and development of OA. Additionally, latent TGF‑β‑binding protein‑1 (LTBP‑1) modulates the activity of the TGF‑β‑mothers against decapentaplegic (Smad) signaling pathway in numerous diseases, including malignant glioma.
View Article and Find Full Text PDFMol Endocrinol
December 2015
Departments of Pathology and Immunology (J.P., P.T.F., D.M., M.M.M.), Molecular and Human Genetics (J.P., P.T.F., M.M.M.), Molecular and Cellular Biology (M.M.M.), and Pharmacology (M.M.M.), Centers for Reproductive Medicine (M.M.M.) and Drug Discovery (P.T.F., D.M., M.M.M.), Baylor College of Medicine, Houston, Texas 77030; Department of Pathology (C.C.), New York University School of Medicine, New York, New York 10016; and Departments of Pathology (G.H.S.) and Otolaryngology/Head and Neck Surgery (G.H.S.), Columbia University College of Physicians and Surgeons, New York, New York 10032.
The placenta is the first organ to develop after fertilization. It forms an interface between the maternal uterus and growing fetus to allow nutrient uptake, waste elimination, and gas exchange for a successful pregnancy in both mice and humans. In the past 2 decades, in vivo and in vitro approaches have been used to show that several members of the TGF-β superfamily regulate embryo implantation and placental development.
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