PMID- 7822413 OWN - NLM STAT- MEDLINE DCOM- 19950214 LR - 20190508 IS - 0021-9525 (Print) IS - 1540-8140 (Electronic) IS - 0021-9525 (Linking) VI - 128 IP - 1-2 DP - 1995 Jan TI - Roles of hepatocyte growth factor/scatter factor and the met receptor in the early development of the metanephros. PG - 171-84 AB - Several lines of evidence suggest that hepatocyte growth factor/scatter factor (HGF/SF), a soluble protein secreted by embryo fibroblasts and several fibroblast lines, may elicit morphogenesis in adjacent epithelial cells. We investigated the role of HGF/SF and its membrane receptor, the product of the c-met protooncogene, in the early development of the metanephric kidney. At the inception of the mouse metanephros at embryonic day 11, HGF/SF was expressed in the mesenchyme, while met was expressed in both the ureteric bud and the mesenchyme, as assessed by reverse transcription PCR, in situ hybridization, and immunohistochemistry. To further investigate the expression of met in renal mesenchyme, we isolated 13 conditionally immortal clonal cell lines from transgenic mice expressing a temperature-sensitive mutant of the SV-40 large T antigen. Five had the HGF/SF+/met+ phenotype and eight had the HGF/SF-/met+ phenotype. None had the HGF/SF+/met- nor the HGF/SF-/met- phenotypes. Thus the renal mesenchyme contains cells that express HGF/SF and met or met alone. When metanephric rudiments were grown in serum-free organ culture, anti-HGF/SF antibodies (a) inhibited the differentiation of metanephric mesenchymal cells into the epithelial precursors of the nephron; (b) increased cell death within the renal mesenchyme; and (c) perturbed branching morphogenesis of the ureteric bud. These data provide the first demonstration for coexpression of the HGF/SF and met genes in mesenchymal cells during embryonic development and also imply an autocrine and/or paracrine role for HGF/SF and met in the survival of the renal mesenchyme and in the mesenchymal-epithelial transition that occurs during nephrogenesis. They also confirm the postulated paracrine role of HGF/SF in the branching of the ureteric bud. FAU - Woolf, A S AU - Woolf AS AD - Units of Developmental Biology and Medicine, Institute of Child Health, London, United Kingdom. FAU - Kolatsi-Joannou, M AU - Kolatsi-Joannou M FAU - Hardman, P AU - Hardman P FAU - Andermarcher, E AU - Andermarcher E FAU - Moorby, C AU - Moorby C FAU - Fine, L G AU - Fine LG FAU - Jat, P S AU - Jat PS FAU - Noble, M D AU - Noble MD FAU - Gherardi, E AU - Gherardi E LA - eng GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Antibodies) RN - 0 (DNA Primers) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 82115-62-6 (Interferon-gamma) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM GS - c-met MH - Animals MH - Antibodies/pharmacology MH - Base Sequence MH - Cell Division/drug effects MH - Cell Line MH - DNA Primers MH - Embryonic and Fetal Development MH - Gene Expression MH - Hepatocyte Growth Factor/analysis/*biosynthesis MH - Interferon-gamma/pharmacology MH - Kidney/cytology/*embryology/*metabolism MH - Kinetics MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Inbred CBA MH - Mice, Transgenic MH - Microscopy, Confocal MH - Molecular Sequence Data MH - Morphogenesis MH - Organ Culture Techniques MH - Polymerase Chain Reaction MH - Proto-Oncogene Proteins c-met MH - Proto-Oncogenes MH - Receptor Protein-Tyrosine Kinases/*biosynthesis MH - Time Factors PMC - PMC2120323 EDAT- 1995/01/01 00:00 MHDA- 1995/01/01 00:01 PMCR- 1995/07/01 CRDT- 1995/01/01 00:00 PHST- 1995/01/01 00:00 [pubmed] PHST- 1995/01/01 00:01 [medline] PHST- 1995/01/01 00:00 [entrez] PHST- 1995/07/01 00:00 [pmc-release] AID - 95122630 [pii] AID - 10.1083/jcb.128.1.171 [doi] PST - ppublish SO - J Cell Biol. 1995 Jan;128(1-2):171-84. doi: 10.1083/jcb.128.1.171.