title: Essential role of HGF (hepatocyte growth factor) in blood formation in Xenopus.
abstract: In this study, we investigated the role of hepatocyte growth factor (HGF) in blood formation during Xenopus development. First, we examined the gene expression of HGF and its receptor, c-met, by whole-mount in situ hybridization during development. Strong signals of HGF as well as c-met were detected early in the developing ventral mesoderm, which later gives rise to the ventral blood island. Furthermore, to study the role of HGF, we blocked the HGF signaling pathway in Xenopus embryos by using truncated c-met lacking the tyrosine kinase domain. Injection of truncated c-met mRNA resulted in a marked decrease in the number of circulating blood cells. Similar results were obtained using morpholino antisense HGF oligonucleotides. Moreover, we also analyzed the expression of several early primitive blood markers in the blood island of these embryos. RNA in situ analysis revealed a significant reduction (or absence) of stem cell leukemia (SCL), alpha-globin, and GATA-1 expression, but not GATA-2 expression. In contrast, no significant difference was observed in the levels of expression of early definitive blood markers, SCL, GATA-2, and GATA-3 in the dorsolateral plate, as analyzed by in situ hybridization. Overall, the present study demonstrated that HGF is necessary for primitive hematopoiesis by regulating the expression of SCL.
authors.affiliation: Division of Gene Therapy, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Koibuchi
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Taniyama
authors.forename: Kunio
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
mesh_terms: D000818:Animals; D001773:Blood Cells; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004625:Embryo, Nonmammalian; D050981:Erythroid-Specific DNA-Binding Factors; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D018507:Gene Expression Regulation, Developmental; D005914:Globins / Q000096:biosynthesis / Q000235:genetics; D006410:Hematopoiesis / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008648:Mesoderm; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D029867:Xenopus Proteins / Q000502:physiology; D014982:Xenopus laevis / Q000196:embryology
chemical_list: D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050989:GATA2 Transcription Factor; C494714:GATA2 protein, Xenopus; D050990:GATA3 Transcription Factor; C494746:GATA3 protein, Xenopus; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C489365:TAL1 protein, Xenopus; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; D017228:Hepatocyte Growth Factor; D005914:Globins; D019859:Proto-Oncogene Proteins c-met