Ndrg1b and fam49ab modulate the PTEN pathway to control T-cell lymphopoiesis in the zebrafish.
During hematopoiesis, the balance between proliferation, differentiation, and apoptosis is tightly regulated in order to maintain homeostasis. Failure in these processes can ultimately lead to uncontrolled proliferation and leukemia. Phosphatase and tensin homolog (PTEN) is one of the molecular pathways involved in this balance. By opposing PI3-kinases, PTEN inhibits proliferation and promotes differentiation and is thus considered a tumor suppressor. Indeed, PTEN is frequently mutated in many cancers, including leukemias. Loss of PTEN often leads to lymphoid cancers. However, little is known about the molecular events that regulate PTEN signaling during lymphopoiesis. In this study, we used zebrafish to address this. We report that N-myc downstream-regulated gene 1b (ndrg1b) rescues lymphoid differentiation after PTEN inhibition. We also show that a previously uncharacterized gene, fam49ab, inhibits T-cell differentiation, a phenotype that can be rescued by ndrg1b We propose that ndrg1b and fam49ab are 2 new modulators of PTEN signaling that control lymphoid differentiation in the zebrafish thymus.
Department of Pathology and Immunology, University of Geneva-School of Medicine, Geneva, Switzerland.
Roman A
RA
Li
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA; and.
David
D
Traver
Hematology Service, University Hospital Geneva, Clinical Pathology Service, Geneva, Switzerland.
Thomas
T
Matthes
Department of Pathology and Immunology, University of Geneva-School of Medicine, Geneva, Switzerland.
Julien Y
JY
Bertrand
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects; D018398:Homeodomain Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D038041:Lymphopoiesis / Q000187:drug effects; D060172:Morpholinos / Q000494:pharmacology; D005810:Multigene Family; D009154:Mutation / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D060168:Thymocytes / Q000187:drug effects / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*; D000099259:N-myc Downstream-Regulated Gene 1 Protein
D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060172:Morpholinos; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D029961:Zebrafish Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C064658:RAG-1 protein