{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T07:53:10Z","timestamp":1775289190099,"version":"3.50.1"},"reference-count":63,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,8,27]],"date-time":"2003-08-27T00:00:00Z","timestamp":1061942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2003,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We investigated the involvement of hepatocyte growth factor (HGF) in salivary gland (SG) branching morphogenesis. The mouse submandibular gland (SMG) starts to develop at embryonic day 11.5\u201312 (E11.5\u2013E12), and branching morphogenesis occurs in the area between the mandibular bone and tongue between E14 and E16.5. Real\u2010time reverse transcriptase\u2010polymerase chain reaction showed that the expression of the <jats:italic>c\u2010met<\/jats:italic>\/HGF receptor gene in SMG increased and peaked between E14 and E16.5, concomitant with epithelial branching, and high levels of HGF mRNA were detected in the surrounding mesenchyme at E14\u2013E15.5. Although strong expression of the HGF and <jats:italic>c\u2010met<\/jats:italic> transcripts was observed in the tongue muscles, this expression was limited at E13.5\u2013E14.5. Serum\u2010free organ cultures were established, in which SG rudiments that contained SMG and sublingual gland (SLG) primordia (explant 1) and SMG\/SLG rudiments with peripheral tissue that included part of the tongue muscle (explant 2) were isolated from E13.5 or E14 embryos. Mesenchyme\u2010free SMG epithelium was obtained by the removal of mesenchymal tissue from explant 1. In the explant 1 and 2 organ cultures, SMG\/SLG rudiments showed growth and branching morphogenesis, while mesenchyme\u2010free epithelium failed to grow. When E13.5 or E14 mesenchyme\u2010free epithelium and a recombinant human HGF (rh\u2010HGF) \u2010soaked bead were placed on Matrigel, the epithelium migrated toward the bead and formed branches, while the E13 epithelium failed to branch. The exogenous application of rh\u2010HGF and anti\u2010HGF antibody to the SMG\/SLG rudiment cultures resulted in stimulation and inhibition, respectively, of branching morphogenesis. However, the response of E13.5 SMG to rh\u2010HGF was very weak, while the branching of E14 SMG was enhanced strongly by rh\u2010HGF. The branching morphogenesis of SMG was also inhibited by the addition of either antisense HGF or <jats:italic>c\u2010met<\/jats:italic> oligodeoxynucleotides to the cultures. The development of SMG in explant 2, which was significantly better than in explant 1, was comparable to that seen in vivo. Moreover, the expression of both HGF and c\u2010Met in the SMG of explant 2 was higher than in the SMG of explant 1. These findings provide the first demonstration that the branching morphogenesis of SMG is regulated by interactions with the surrounding mesenchyme\u2010derived HGF and <jats:italic>c\u2010met<\/jats:italic> expression in SMG, which occur concomitant with epithelial branching. The present data also suggest that the HGF that is released transiently from tongue muscles may contribute to the rapid development of SMG at the branching stage. Developmental Dynamics 228:173\u2013184, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.10377","type":"journal-article","created":{"date-parts":[[2003,9,25]],"date-time":"2003-09-25T05:40:35Z","timestamp":1064468435000},"page":"173-184","source":"Crossref","is-referenced-by-count":30,"title":["Involvement of hepatocyte growth factor in branching morphogenesis of murine salivary 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