FGF7 signals are relayed to autocrine EGF family growth factors to induce branching morphogenesis of mouse salivary epithelium.
BACKGROUND
The Matrigel-embedded epithelium of the mouse submandibular gland undergoes branching morphogenesis when cultured in medium supplemented with fibroblast growth factor 7 (FGF7) and lysophosphatidic acid (LPA), whereas it elongates a stalk with limited branching in medium with only FGF7. Because LPA is a well-known activator of epidermal growth factor (EGF) signaling, we hypothesized the involvement of autocrine EGF family growth factors in the branching morphogenesis.


RESULTS
Reverse transcriptase polymerase chain reaction studies showed that three members, Tgfa, Hbegf,and Nrg1 of the EGF family were expressed in the epithelium cultured with FGF7 + LPA as well as in the epithelium freshly isolated from the rudiments. All the growth factors induced extensive branching morphogenesis in the Matrigel-embedded epithelium in the presence of LPA. Tyrphostin AG112, an inhibitor of EGF signaling, severely impaired branching morphogenesis induced by FGF7 + LPA without exogenous addition of EGF family growth factors to the culture medium. The shaking cultures, which were expected to decrease the concentration of autocrine growth factors near the epithelium by promoting their diffusion, significantly reduced branching morphogenesis induced by FGF7 + LPA.


CONCLUSIONS
Autocrine EGF family growth factors are involved in epithelial branching morphogenesis induced by FGF7 + LPA.
Department of Biology, Graduate School of Science, Chiba University, Chiba, Japan.
Hayashi
H
Kera
Satoshi
S
Yuki
Hiroyuki
H
Nogawa
D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D004848:Epithelium / Q000196:embryology; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism* / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice; D009024:Morphogenesis / Q000187:drug effects / Q000502:physiology*; D012469:Salivary Glands / Q000166:cytology / Q000196:embryology*
C496454:Fgf7 protein, mouse; D008246:Lysophospholipids; D051523:Fibroblast Growth Factor 7; D004815:Epidermal Growth Factor; C032881:lysophosphatidic acid
EGF family growth factors; autocrine signaling; branching morphogenesis; mouse; submandibular gland