{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T15:39:39Z","timestamp":1780933179914,"version":"3.54.1"},"reference-count":55,"publisher":"The Company of Biologists","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,3,15]]},"abstract":"<jats:p>Branching morphogenesis of mouse submandibular glands is regulated by multiple growth factors. Here, we report that ex vivo branching of intact submandibular glands decreases when either FGFR2 expression is downregulated or soluble recombinant FGFR2b competes out the endogenous growth factors. However, a combination of neutralizing antibodies to FGF1, FGF7 and FGF10 is required to inhibit branching in the intact gland, suggesting that multiple FGF isoforms are required for branching. Exogenous FGFs added to submandibular epithelial rudiments cultured without mesenchyme induce distinct morphologies. FGF7 induces epithelial budding, whereas FGF10 induces duct elongation, and both are inhibited by FGFR or ERK1\/2 signaling inhibitors. However, a PI3-kinase inhibitor also decreases FGF7-mediated epithelial budding, suggesting that multiple signaling pathways exist. We immunolocalized FGF receptors and analyzed changes in FGFR, FGF and MMP gene expression to identify the mechanisms of FGF-mediated morphogenesis. FGFR1b and FGFR2b are present throughout the epithelium,although FGFR1b is more highly expressed around the periphery of the buds and the duct tips. FGF7 signaling increases FGFR1b and FGF1expression, and MMP2 activity, when compared with FGF10, resulting in increased cell proliferation and expansion of the epithelial bud, whereas FGF10 stimulates localized proliferation at the tip of the duct. FGF7- and FGF10-mediated morphogenesis is inhibited by an MMP inhibitor and a neutralizing antibody to FGF1, suggesting that both FGF1 and MMPs are essential downstream mediators of epithelial morphogenesis. Taken together,our data suggests that FGFR2b signaling involves a regulatory network of FGFR1b\/FGF1\/MMP2 expression that mediates budding and duct elongation during branching morphogenesis.<\/jats:p>","DOI":"10.1242\/dev.01690","type":"journal-article","created":{"date-parts":[[2005,2,17]],"date-time":"2005-02-17T01:24:27Z","timestamp":1108603467000},"page":"1223-1234","source":"Crossref","is-referenced-by-count":235,"title":["FGFR2b signaling regulates ex vivo submandibular gland epithelial cell proliferation and branching morphogenesis"],"prefix":"10.1242","volume":"132","author":[{"given":"Zachary","family":"Steinberg","sequence":"first","affiliation":[{"name":"Matrix and Morphogenesis Unit, Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research,National Institutes of Health, 30 Convent Drive, MSC 4370, Bethesda, MD 20892-4370, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Myers","sequence":"additional","affiliation":[{"name":"Matrix and Morphogenesis Unit, Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research,National Institutes of Health, 30 Convent Drive, MSC 4370, Bethesda, MD 20892-4370, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vernon M.","family":"Heim","sequence":"additional","affiliation":[{"name":"Matrix and Morphogenesis Unit, Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research,National Institutes of Health, 30 Convent Drive, MSC 4370, Bethesda, MD 20892-4370, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin A.","family":"Lathrop","sequence":"additional","affiliation":[{"name":"Matrix and Morphogenesis Unit, Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research,National Institutes of Health, 30 Convent Drive, MSC 4370, Bethesda, MD 20892-4370, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan T.","family":"Rebustini","sequence":"additional","affiliation":[{"name":"Matrix and Morphogenesis Unit, Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research,National Institutes of Health, 30 Convent Drive, MSC 4370, Bethesda, MD 20892-4370, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian S.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Matrix and Morphogenesis Unit, Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research,National Institutes of Health, 30 Convent Drive, MSC 4370, Bethesda, MD 20892-4370, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"Larsen","sequence":"additional","affiliation":[{"name":"Matrix and Morphogenesis Unit, Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research,National Institutes of Health, 30 Convent Drive, MSC 4370, Bethesda, MD 20892-4370, USA"},{"name":"Developmental Mechanisms Section, Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research,National Institutes of Health, 30 Convent Drive, MSC 4370, Bethesda, MD 20892-4370, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Matrix and Morphogenesis Unit, Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research,National Institutes of Health, 30 Convent Drive, MSC 4370, Bethesda, MD 20892-4370, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042605360348200_REF1","doi-asserted-by":"crossref","unstructured":"Bellusci, S., Grindley, J., Emoto, H., Itoh, N. and Hogan, B. L. (1997). Fibroblast growth factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung. Development124,4867-4878.","DOI":"10.1242\/dev.124.23.4867"},{"key":"2021042605360348200_REF2","doi-asserted-by":"crossref","unstructured":"Boilly, B., Vercoutter-Edouart, A. S., Hondermarck, H.,Nurcombe, V. and Le Bourhis, X. (2000). FGF signals for cell proliferation and migration through different pathways. Cytokine Growth Factor Rev.11,295-302.","DOI":"10.1016\/S1359-6101(00)00014-9"},{"key":"2021042605360348200_REF3","doi-asserted-by":"crossref","unstructured":"Cardoso, W. V., Itoh, A., Nogawa, H., Mason, I. and Brody, J. S. (1997). FGF-1 and FGF-7 induce distinct patterns of growth and differentiation in embryonic lung epithelium. Dev. Dyn.208,398-405.","DOI":"10.1002\/(SICI)1097-0177(199703)208:3<398::AID-AJA10>3.0.CO;2-X"},{"key":"2021042605360348200_REF4","doi-asserted-by":"crossref","unstructured":"Celli, G., LaRochelle, W. J., Mackem, S., Sharp, R. and Merlino,G. (1998). Soluble dominant-negative receptor uncovers essential roles for fibroblast growth factors in multi-organ induction and patterning. EMBO J.17,1642-1655.","DOI":"10.1093\/emboj\/17.6.1642"},{"key":"2021042605360348200_REF5","doi-asserted-by":"crossref","unstructured":"Chandrasekher, G., Kakazu, A. H. and Bazan, H. E.(2001). HGF- and KGF-induced activation of PI-3K\/p70 s6 kinase pathway in corneal epithelial cells: its relevance in wound healing. Exp. Eye Res.73,191-202.","DOI":"10.1006\/exer.2001.1026"},{"key":"2021042605360348200_REF6","doi-asserted-by":"crossref","unstructured":"De Moerlooze, L., Spencer-Dene, B., Revest, J., Hajihosseini,M., Rosewell, I. and Dickson, C. (2000). An important role for the IIIb isoform of fibroblast growth factor receptor 2 (FGFR2) in mesenchymal-epithelial signalling during mouse organogenesis. Development127,483-492.","DOI":"10.1242\/dev.127.3.483"},{"key":"2021042605360348200_REF7","doi-asserted-by":"crossref","unstructured":"Govindarajan, V., Ito, M., Makarenkova, H. P., Lang, R. A. and Overbeek, P. A. (2000). Endogenous and ectopic gland induction by FGF-10. Dev. Biol.225,188-200.","DOI":"10.1006\/dbio.2000.9812"},{"key":"2021042605360348200_REF8","doi-asserted-by":"crossref","unstructured":"Guo, L., Yu, Q. C. and Fuchs, E. (1993). Targeting expression of keratinocyte growth factor to keratinocytes elicits striking changes in epithelial differentiation in transgenic mice. EMBO J.12,973-986.","DOI":"10.1002\/j.1460-2075.1993.tb05738.x"},{"key":"2021042605360348200_REF9","doi-asserted-by":"crossref","unstructured":"Guo, L., Degenstein, L. and Fuchs, E. (1996). Keratinocyte growth factor is required for hair development but not for wound healing. Genes Dev.10,165-175.","DOI":"10.1101\/gad.10.2.165"},{"key":"2021042605360348200_REF10","doi-asserted-by":"crossref","unstructured":"Harada, H., Toyono, T., Toyoshima, K., Yamasaki, M., Itoh, N.,Kato, S., Sekine, K. and Ohuchi, H. (2002). FGF10 maintains stem cell compartment in developing mouse incisors. Development129,1533-1541.","DOI":"10.1242\/dev.129.6.1533"},{"key":"2021042605360348200_REF11","unstructured":"Hayakawa, T., Kishi, J. and Nakanishi, Y.(1992). Salivary gland morphogenesis: possible involvement of collagenase. Matrix Suppl.1, 344-351."},{"key":"2021042605360348200_REF12","doi-asserted-by":"crossref","unstructured":"Hoffman, M. P., Kidder, B. L., Steinberg, Z. L., Lakhani, S.,Ho, S., Kleinman, H. K. and Larsen, M. (2002). Gene expression profiles of mouse submandibular gland development: FGFR1 regulates branching morphogenesis in vitro through BMP- and FGF-dependent mechanisms. Development129,5767-5778.","DOI":"10.1242\/dev.00172"},{"key":"2021042605360348200_REF13","doi-asserted-by":"crossref","unstructured":"Holmbeck, K., Bianco, P., Caterina, J., Yamada, S., Kromer,M., Kuznetsov, S. A., Mankani, M., Robey, P. G., Poole, A. R., Pidoux,I. et al. (1999). MT1-MMP-deficient mice develop dwarfism,osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell99, 81-92.","DOI":"10.1016\/S0092-8674(00)80064-1"},{"key":"2021042605360348200_REF14","doi-asserted-by":"crossref","unstructured":"Igarashi, M., Finch, P. W. and Aaronson, S. A.(1998). Characterization of recombinant human fibroblast growth factor (FGF)-10 reveals functional similarities with keratinocyte growth factor (FGF-7). J. Biol. Chem.273,13230-13235.","DOI":"10.1074\/jbc.273.21.13230"},{"key":"2021042605360348200_REF15","doi-asserted-by":"crossref","unstructured":"Itoh, T., Ikeda, T., Gomi, H., Nakao, S., Suzuki, T. and Itohara, S. (1997). Unaltered secretion of beta-amyloid precursor protein in gelatinase A (matrix metalloproteinase 2)-deficient mice. J. Biol. Chem.272,22389-22392.","DOI":"10.1074\/jbc.272.36.22389"},{"key":"2021042605360348200_REF16","doi-asserted-by":"crossref","unstructured":"Izvolsky, K. I., Shoykhet, D., Yang, Y., Yu, Q., Nugent, M. A. and Cardoso, W. V. (2003a). Heparan sulfate-FGF10 interactions during lung morphogenesis. Dev. Biol.258,185-200.","DOI":"10.1016\/S0012-1606(03)00114-3"},{"key":"2021042605360348200_REF17","doi-asserted-by":"crossref","unstructured":"Izvolsky, K. I., Zhong, L., Wei, L., Yu, Q., Nugent, M. A. and Cardoso, W. V. (2003b). Heparan sulfates expressed in the distal lung are required for Fgf10 binding to the epithelium and for airway branching. Am. J. Physiol. Lung Cell Mol. Physiol.285,L838-L846.","DOI":"10.1152\/ajplung.00081.2003"},{"key":"2021042605360348200_REF18","doi-asserted-by":"crossref","unstructured":"Jaskoll, T. and Melnick, M. (1999). Submandibular gland morphogenesis: stage-specific expression of TGF-alpha\/EGF,IGF, TGF-beta, TNF, and IL-6 signal transduction in normal embryonic mice and the phenotypic effects of TGF-beta2, TGF-beta3, and EGF-r null mutations. Anat. Rec.256,252-268.","DOI":"10.1002\/(SICI)1097-0185(19991101)256:3<252::AID-AR5>3.0.CO;2-6"},{"key":"2021042605360348200_REF19","doi-asserted-by":"crossref","unstructured":"Jaskoll, T., Zhou, Y. M., Chai, Y., Makarenkova, H. P.,Collinson, J. M., West, J. D., Hajihosseini, M. K., Lee, J. and Melnick, M. (2002). Embryonic submandibular gland morphogenesis: stage-specific protein localization of FGFs, BMPs, Pax6 and Pax9 in normal mice and abnormal SMG phenotypes in FgfR2-IIIc(+\/Delta),BMP7(-\/-) and Pax6(-\/-) mice. Cells Tissues Organs170, 83-98.","DOI":"10.1159\/000046183"},{"key":"2021042605360348200_REF20","doi-asserted-by":"crossref","unstructured":"Jaskoll, T., Witcher, D., Toreno, L., Bringas, P., Moon, A. M. and Melnick, M. (2004). FGF8 dose-dependent regulation of embryonic submandibular salivary gland morphogenesis. Dev. Biol.268,457-469.","DOI":"10.1016\/j.ydbio.2004.01.004"},{"key":"2021042605360348200_REF21","doi-asserted-by":"crossref","unstructured":"Kashimata, M. and Gresik, E. W. (1997). Epidermal growth factor system is a physiological regulator of development of the mouse fetal submandibular gland and regulates expression of the alpha6-integrin subunit. Dev. Dyn.208,149-161.","DOI":"10.1002\/(SICI)1097-0177(199702)208:2<149::AID-AJA2>3.0.CO;2-I"},{"key":"2021042605360348200_REF22","doi-asserted-by":"crossref","unstructured":"Kashimata, M., Sayeed, S., Ka, A., Onetti-Muda, A., Sakagami,H., Faraggiana, T. and Gresik, E. W. (2000). The ERK-1\/2 signaling pathway is involved in the stimulation of branching morphogenesis of fetal mouse submandibular glands by EGF. Dev. Biol.220,183-196.","DOI":"10.1006\/dbio.2000.9639"},{"key":"2021042605360348200_REF23","doi-asserted-by":"crossref","unstructured":"Kettunen, P., Laurikkala, J., Itaranta, P., Vainio, S., Itoh, N. and Thesleff, I. (2000). Associations of FGF-3 and FGF-10 with signaling networks regulating tooth morphogenesis. Dev. Dyn.219,322-332.","DOI":"10.1002\/1097-0177(2000)9999:9999<::AID-DVDY1062>3.0.CO;2-J"},{"key":"2021042605360348200_REF24","doi-asserted-by":"crossref","unstructured":"Larsen, M., Hoffman, M. P., Sakai, T., Neibaur, J. C., Mitchell,J. M. and Yamada, K. M. (2003). Role of PI 3-kinase and PIP3 in submandibular gland branching morphogenesis. Dev. Biol.255,178-191.","DOI":"10.1016\/S0012-1606(02)00047-7"},{"key":"2021042605360348200_REF25","doi-asserted-by":"crossref","unstructured":"Lebeche, D., Malpel, S. and Cardoso, W. V.(1999). Fibroblast growth factor interactions in the developing lung. Mech. Dev.86,125-136.","DOI":"10.1016\/S0925-4773(99)00124-0"},{"key":"2021042605360348200_REF26","doi-asserted-by":"crossref","unstructured":"Levi, E., Fridman, R., Miao, H. Q., Ma, Y. S., Yayon, A. and Vlodavsky, I. (1996). Matrix metalloproteinase 2 releases active soluble ectodomain of fibroblast growth factor receptor 1. Proc. Natl. Acad. Sci. USA93,7069-7074.","DOI":"10.1073\/pnas.93.14.7069"},{"key":"2021042605360348200_REF27","doi-asserted-by":"crossref","unstructured":"Liu, J. F., Crepin, M., Liu, J. M., Barritault, D. and Ledoux,D. (2002). FGF-2 and TPA induce matrix metalloproteinase-9 secretion in MCF-7 cells through PKC activation of the Ras\/ERK pathway. Biochem. Biophys. Res. Commun.293,1174-1182.","DOI":"10.1016\/S0006-291X(02)00350-9"},{"key":"2021042605360348200_REF28","doi-asserted-by":"crossref","unstructured":"Makarenkova, H. P., Ito, M., Govindarajan, V., Faber, S. C.,Sun, L., McMahon, G., Overbeek, P. A. and Lang, R. A.(2000). FGF10 is an inducer and Pax6 a competence factor for lacrimal gland development. Development127,2563-2572.","DOI":"10.1242\/dev.127.12.2563"},{"key":"2021042605360348200_REF29","doi-asserted-by":"crossref","unstructured":"Martin, G. R. (1998). The roles of FGFs in the early development of vertebrate limbs. Genes Dev.12,1571-1586.","DOI":"10.1101\/gad.12.11.1571"},{"key":"2021042605360348200_REF30","doi-asserted-by":"crossref","unstructured":"Min, H., Danilenko, D. M., Scully, S. A., Bolon, B., Ring, B. D., Tarpley, J. E., DeRose, M. and Simonet, W. S.(1998). Fgf-10 is required for both limb and lung development and exhibits striking functional similarity to Drosophila branchless. Genes Dev.12,3156-3161.","DOI":"10.1101\/gad.12.20.3156"},{"key":"2021042605360348200_REF31","doi-asserted-by":"crossref","unstructured":"Miura, T. and Shiota, K. (2002). Depletion of FGF acts as a lateral inhibitory factor in lung branching morphogenesis in vitro. Mech. Dev.116,29-38.","DOI":"10.1016\/S0925-4773(02)00132-6"},{"key":"2021042605360348200_REF32","doi-asserted-by":"crossref","unstructured":"Morita, K. and Nogawa, H. (1999). EGF-dependent lobule formation and FGF7-dependent stalk elongation in branching morphogenesis of mouse salivary epithelium in vitro. Dev. Dyn.215,148-154.","DOI":"10.1002\/(SICI)1097-0177(199906)215:2<148::AID-DVDY7>3.0.CO;2-V"},{"key":"2021042605360348200_REF33","doi-asserted-by":"crossref","unstructured":"Nakanishi, Y., Sugiura, F., Kishi, J. and Hayakawa, T.(1986). Collagenase inhibitor stimulates cleft formation during early morphogenesis of mouse salivary gland. Dev. Biol.113,201-206.","DOI":"10.1016\/0012-1606(86)90122-3"},{"key":"2021042605360348200_REF34","doi-asserted-by":"crossref","unstructured":"Neubuser, A., Peters, H., Balling, R. and Martin, G. R.(1997). Antagonistic interactions between FGF and BMP signaling pathways: a mechanism for positioning the sites of tooth formation. Cell90,247-255.","DOI":"10.1016\/S0092-8674(00)80333-5"},{"key":"2021042605360348200_REF35","doi-asserted-by":"crossref","unstructured":"Niswander, L. and Martin, G. R. (1993). FGF-4 and BMP-2 have opposite effects on limb growth. Nature361, 68-71.","DOI":"10.1038\/361068a0"},{"key":"2021042605360348200_REF36","doi-asserted-by":"crossref","unstructured":"Oh, J., Takahashi, R., Adachi, E., Kondo, S., Kuratomi, S.,Noma, A., Alexander, D. B., Motoda, H., Okada, A., Seiki, M. et al.(2004). Mutations in two matrix metalloproteinase genes, MMP-2 and MT1-MMP, are synthetic lethal in mice. Oncogene23,5041-5048.","DOI":"10.1038\/sj.onc.1207688"},{"key":"2021042605360348200_REF37","doi-asserted-by":"crossref","unstructured":"Ohuchi, H., Hori, Y., Yamasaki, M., Harada, H., Sekine, K.,Kato, S. and Itoh, N. (2000). FGF10 acts as a major ligand for FGF receptor 2 IIIb in mouse multi-organ development. Biochem. Biophys. Res. Commun.277,643-649.","DOI":"10.1006\/bbrc.2000.3721"},{"key":"2021042605360348200_REF38","doi-asserted-by":"crossref","unstructured":"Ornitz, D. M. (2000). FGFs, heparan sulfate and FGFRs: complex interactions essential for development. BioEssays22,108-112.","DOI":"10.1002\/(SICI)1521-1878(200002)22:2<108::AID-BIES2>3.0.CO;2-M"},{"key":"2021042605360348200_REF39","doi-asserted-by":"crossref","unstructured":"Ornitz, D. M. and Itoh, N. (2001). Fibroblast growth factors. Genome Biol.2,REVIEWS3005.","DOI":"10.1186\/gb-2001-2-3-reviews3005"},{"key":"2021042605360348200_REF40","doi-asserted-by":"crossref","unstructured":"Pohl, M., Sakurai, H., Bush, K. T. and Nigam, S. K.(2000). Matrix metalloproteinases and their inhibitors regulate in vitro ureteric bud branching morphogenesis. Am. J. Physiol. Renal Physiol.279,F891-F900.","DOI":"10.1152\/ajprenal.2000.279.5.F891"},{"key":"2021042605360348200_REF41","doi-asserted-by":"crossref","unstructured":"Post, M., Souza, P., Liu, J., Tseu, I., Wang, J., Kuliszewski,M. and Tanswell, A. K. (1996). Keratinocyte growth factor and its receptor are involved in regulating early lung branching. Development122,3107-3115.","DOI":"10.1242\/dev.122.10.3107"},{"key":"2021042605360348200_REF42","doi-asserted-by":"crossref","unstructured":"Powers, C. J., McLeskey, S. W. and Wellstein, A.(2000). Fibroblast growth factors, their receptors and signaling. Endocr. Relat. Cancer7,165-197.","DOI":"10.1677\/erc.0.0070165"},{"key":"2021042605360348200_REF43","doi-asserted-by":"crossref","unstructured":"Qiao, J., Uzzo, R., Obara-Ishihara, T., Degenstein, L., Fuchs,E. and Herzlinger, D. (1999). FGF-7 modulates ureteric bud growth and nephron number in the developing kidney. Development126,547-554.","DOI":"10.1242\/dev.126.3.547"},{"key":"2021042605360348200_REF44","doi-asserted-by":"crossref","unstructured":"Qiao, J., Bush, K. T., Steer, D. L., Stuart, R. O., Sakurai, H.,Wachsman, W. and Nigam, S. K. (2001). Multiple fibroblast growth factors support growth of the ureteric bud but have different effects on branching morphogenesis. Mech. Dev.109,123-135.","DOI":"10.1016\/S0925-4773(01)00592-5"},{"key":"2021042605360348200_REF45","doi-asserted-by":"crossref","unstructured":"Schmahl, J., Kim, Y., Colvin, J. S., Ornitz, D. M. and Capel,B. (2004). Fgf9 induces proliferation and nuclear localization of FGFR2 in Sertoli precursors during male sex determination. Development131,3627-3636.","DOI":"10.1242\/dev.01239"},{"key":"2021042605360348200_REF46","doi-asserted-by":"crossref","unstructured":"Sekine, K., Ohuchi, H., Fujiwara, M., Yamasaki, M., Yoshizawa,T., Sato, T., Yagishita, N., Matsui, D., Koga, Y., Itoh, N. et al.(1999). Fgf10 is essential for limb and lung formation. Nat. Genet.21,138-141.","DOI":"10.1038\/5096"},{"key":"2021042605360348200_REF47","doi-asserted-by":"crossref","unstructured":"Simian, M., Hirai, Y., Navre, M., Werb, Z., Lochter, A. and Bissell, M. J. (2001). The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells. Development128,3117-3131.","DOI":"10.1242\/dev.128.16.3117"},{"key":"2021042605360348200_REF48","doi-asserted-by":"crossref","unstructured":"Sun, X., Mariani, F. V. and Martin, G. R.(2002). Functions of FGF signalling from the apical ectodermal ridge in limb development. Nature418,501-508.","DOI":"10.1038\/nature00902"},{"key":"2021042605360348200_REF49","doi-asserted-by":"crossref","unstructured":"Tsang, M. and Dawid, I. B. (2004). Promotion and attenuation of FGF signaling through the Ras-MAPK pathway. Sci STKE2004,pe17.","DOI":"10.1126\/stke.2282004pe17"},{"key":"2021042605360348200_REF50","doi-asserted-by":"crossref","unstructured":"Uhlmann, E., Peyman, A., Ryte, A., Schmidt, A. and Buddecke,E. (2000). Use of minimally modified antisense oligonucleotides for specific inhibition of gene expression. Meth. Enzymol.313,268-284.","DOI":"10.1016\/S0076-6879(00)13017-4"},{"key":"2021042605360348200_REF51","doi-asserted-by":"crossref","unstructured":"Weaver, M., Dunn, N. R. and Hogan, B. L.(2000). Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis. Development127,2695-2704.","DOI":"10.1242\/dev.127.12.2695"},{"key":"2021042605360348200_REF52","doi-asserted-by":"crossref","unstructured":"Wells, A. and Marti, U. (2002). Signalling shortcuts: cell-surface receptors in the nucleus? Nat. Rev. Mol. Cell. Biol.3,697-702.","DOI":"10.1038\/nrm905"},{"key":"2021042605360348200_REF53","doi-asserted-by":"crossref","unstructured":"Yeh, B. K., Igarashi, M., Eliseenkova, A. V., Plotnikov, A. N.,Sher, I., Ron, D., Aaronson, S. A. and Mohammadi, M.(2003). Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors. Proc. Natl. Acad. Sci. USA100,2266-2271.","DOI":"10.1073\/pnas.0436500100"},{"key":"2021042605360348200_REF54","unstructured":"Zang, X. P., Lerner, M. R., Dunn, S. T., Brackett, D. J. and Pento, J. T. (2003). Antisense KGFR oligonucleotide inhibition of KGF-induced motility in breast cancer cells. Anticancer Res.23,4913-4919."},{"key":"2021042605360348200_REF55","doi-asserted-by":"crossref","unstructured":"Zhou, M., Sutliff, R. L., Paul, R. J., Lorenz, J. N., Hoying, J. B., Haudenschild, C. C., Yin, M., Coffin, J. D., Kong, L., Kranias, E. G. et al. (1998). Fibroblast growth factor 2 control of vascular tone. Nat. Med.4, 201-207.","DOI":"10.1038\/nm0298-201"}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/132\/6\/1223\/1544581\/1223.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/132\/6\/1223\/1544581\/1223.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T05:42:41Z","timestamp":1683006161000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/132\/6\/1223\/43347\/FGFR2b-signaling-regulates-ex-vivo-submandibular"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,3,15]]},"references-count":55,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2005,3,15]]}},"URL":"https:\/\/doi.org\/10.1242\/dev.01690","relation":{},"ISSN":["1477-9129","0950-1991"],"issn-type":[{"value":"1477-9129","type":"electronic"},{"value":"0950-1991","type":"print"}],"subject":[],"published":{"date-parts":[[2005,3,15]]}}}