Journal Mobile Options
Table of Contents
Vol. 170, No. 2-3, 2002
Issue release date: 2002
Cells Tissues Organs 2002;170:83–98
(DOI:10.1159/000046183)

Embryonic Submandibular Gland Morphogenesis: Stage-Specific Protein Localization of FGFs, BMPs, Pax6 and Pax9 in Normal Mice and Abnormal SMG Phenotypes in FgfR2-IIIc+/Δ, BMP7–/– and Pax6–/–Mice

Jaskoll T. · Zhou Y.M. · Chai Y. · Makarenkova H.P. · Collinson J.M. · West J.D. · Hajihosseini M.K. · Lee J. · Melnick M.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Embryonic submandibular salivary gland (SMG) initiation and branching morphogenesis are dependent on cell-cell communications between and within epithelium and mesenchyme. Such communications are typically mediated in other organs (teeth, lung, lacrimal glands) by growth factors in such a way as to translate autocrine, juxtacrine and paracrine signals into specific gene responses regulating cell division and histodifferentiation. Using Wnt1-Cre/R26R transgenic mice, we demonstrate that embryonic SMG mesenchyme is derived exclusively from cranial neural crest. This origin contrasts to that known for tooth mesenchyme, previously shown to be derived from both neural crest and nonneural crest cells. Thus, although both SMGs and teeth are mandibular derivatives, we can expect overlap and differences in the details of their early inductive interactions. In addition, since embryonic SMG branching morphogenesis is analogous to that seen in other branching organs, we also expect similarities of expression regarding those molecules known to be ubiquitous regulators of morphogenesis. In this study, we performed an analysis of the distribution of specific fibroblast growth factors (FGFs), FGF receptors, bone morphogenetic proteins (BMPs) and Pax transcription factors, previously shown to be important for tooth development and/or branching morphogenesis, from the time of initiation of embryonic SMG development until early branching morphogenesis. In addition, we report abnormal SMG phenotypes in FgfR2- IIIc+/Δ, BMP7–/–and Pax6–/– mice. Our results, in comparison with functional studies in other systems, suggest that FGF-2/FGFR-1, FGF-8/FGFR-2(IIIc) and FGF-10/FGFR-2(IIIb) signaling have different paracrine and juxtacrine functions during SMG initial bud formation and branching. Finally, our observations of abnormal SMGs in BMP7–/– and Pax6–/–indicate that both BMP7 and Pax6 play important roles during embryonic SMG branching morphogenesis.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Callaerts, P., G. Halder, W.J. Gehring (1997) PAX-6 in development and evolution. Annu Rev Neurosci 20: 483–532.
  2. Caric, D., D. Gooday, R.E. Hill, S.K. McConnell, D.J. Price (1997) Determination of the migratory capacity of embryonic cortical cells lacking the transcription factor Pax-6. Development 124: 5087–5096.

    External Resources

  3. Celli, G., W.J. LaRochelle, S. Mackem, R. Sharp, G. Merlino (1998) Soluble dominant-negative receptor uncovers essential roles for fibroblast growth factors in multi-organ induction and patterning. EMBO J 17: 1642–1655.
  4. Chai, Y., X. Jiang, Y. Ito, P. Bringas, J. Han, D.H. Rowitch, P. Soriano, A.P. McMahon, H.M. Sucov (2000) Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis. Development 127: 1671–1679.
  5. Chapouton, P., A. Gartner, M. Gotz (1999) The role of Pax6 in restricting cell migration between developing cortex and basal ganglia. Development 126: 5569–5579.
  6. Collinson, J.M., R.E. Hill, J.D. West (2000) Different roles for Pax6 in the optic vesicle and facial epithelium mediate early morphogenesis of the murine eye. Development 127: 945–956.

    External Resources

  7. Cutler, L.S. (1990) The role of extracellular matrix in the morphogenesis and differentiation of salivary glands. Adv Dent Res 4: 27–33.
  8. Danielian, P.S., D. Muccino, D.H. Rowitch, S.K. Michael, A.P. McMahon (1998) Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible from of Cre recombinase. Curr Biol 8: 1323–1326.
  9. De Moerlooze, L., B. Spencer-Dene, J.-M. Revest, M. Hajihosseini, I. Rosewell, C. Dickson (2000) An important role for the IIIb isoform of fibroblast growth factor receptor 2 (FGFR2) in mesenchymal-epithelial signaling during mouse organogenesis. Development 127: 483–492.
  10. Deng, C.X., A. Wynshaw-Boris, M.M. Shen, C. Daugherty, D.M. Ornitz, P. Leder (1994) Murine FGFR-1 is required for early postimplantation growth and axial organization. Genes Dev 8: 3045–3057.
  11. Dudley, A.T., R.E. Godin, E.J. Robertson (1999) Interaction between FGF and BMP signaling pathways regulates development of metanephric mesenchyme. Genes Dev 13: 1601–1613.
  12. Dudley, A.T., E.J. Robertson (1997) Overlapping expression domains of bone morphogenetic protein family members potentially account for limited tissue defects in BMP7 deficient proteins. Dev Dyn 208: 349–362.
  13. Duncan, M.K., Z. Kozmik, K. Cveklova, J. Piatigorsky, A. Cvekl (2000) Overexpression of Pax6(5a) in lens fiber cells results in cataract and upregulation of (α)5(β)1 integrin expression. J Cell Sci 113: 3173–3185.

    External Resources

  14. Engelkamp, D., P. Rashbass, A. Seawright, V. van Heyningen (1999) Role of Pax6 in development of the cerebellar system. Development 126: 3585–3596.

    External Resources

  15. Furuta, Y., B.L.M. Hogan (1998) BMP4 is essential for lens induction in the mouse embryo. Genes Dev 12: 3764–3775.

    External Resources

  16. Grindley, J.C., D.R. Davidson, R.E. Hill (1995) The role of Pax-6 in eye and nasal development. Development 121: 1433–1442.

    External Resources

  17. Guo, L., L. Degenstein, E. Fuchs (1996) Keratinocyte growth factor is required for hair development but not for wound healing. Genes Dev 10: 165–175.
  18. Hajihosseini, M.K., S. Wilson, L. De Moerlooze, C. Dickson (2001) A splicing switch and gain of function mutation in FgfR2-IIIc hemizygotes causes Apert/Pfeiffer-like phenotypes. Proc Natl Acad Sci USA 98: 3855–3861.
  19. Hill, R.E., J. Favor, B.L.M. Hogan, C.C.T. Ton, G.F. Saunders, I.M. Hansom, J. Prosser, T. Jordan, N.D. Hastie, V. van Heyningen (1991) Mouse small eye results from mutations in a paired-like homeobox-containing gene. Nature 354: 399–413.
  20. Hogan, B.L.M. (1999) Morphogenesis. Cell 96: 225–233.
  21. Igarashi, M., P.W. Finch, S.A. Aaronson (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.
  22. Jackson, D., J. Bresnick, I. Rosewell, T. Crafton, R. Poulsom, G. Stamp, C. Dickson (1997) Fibroblast growth factor receptor signaling has a role in lobuloalveolar development of the mammary gland. J Cell Sci 110: 1261–1268.

    External Resources

  23. Jaskoll, T., M. Melnick (1999) Submandibular gland morphogenesis: Stage-specific expression of TGF-α/EGF, IGF, TGF-β, TNF, and IL-6 signal transduction in normal embryonic mice and the phenotypic effects of TGF-β2, TGF-β3 and EGF-R null mutations. Anat Rec 256: 252–268.
  24. Jaskoll, T., H.A. Choy, M. Melnick (1994) Glucocorticoids, TGF-beta, and embryonic mouse salivary gland morphogenesis. J Craniofac Genet Dev Biol 14: 217–230.

    External Resources

  25. Jernvall, J., I. Thesleff (2000) Reiterative signaling and patterning during mammalian tooth morphogenesis. Mech Dev 92: 19–29.
  26. Kaufman, M.H., H.-H. Chang, J.P. Shaw (1995) Craniofacial abnormalities in homozygous Small eye (Sey/Sey) embryos and newborn mice. J Anat 186: 607–617.

    External Resources

  27. Kioussi, C., S. O’Connell, L. St-Onge, M. Treier, A.S. Gleiberman, P. Gruss, M.G. Rosenfeld (1999) Pax6 is essential for establishing ventral-dorsal cell boundaries in pituitary gland development. Proc Natl Acad Sci USA 96: 14378–14382.
  28. Kuure, S., R. Vuolteenaho, S. Vainio (2000) Kidney morphogenesis: Cellular and molecular regulation. Mech Dev 92: 31–45.
  29. Lebeche, D., S. Malpel, W.V. Cardoso (1999) Fibroblast growth factor interactions in the developing lung. Mech Dev 86: 125–136.

    External Resources

  30. Le Douarin, N., C. Ziller, G. Coul (1993) Patterning of neural crest derivatives in the avian embryo: In vivo and in vitro studies. Dev Biol 159: 24–49.
  31. MacArthur, C.A., A. Lawshe, J. Xu, S. Santos-Ocampo, M. Heikinheimo, A.T. Chellaiah, D.M. Ornitz (1995) FGF-8 isoforms activate receptor splice forms that are expressed in mesenchymal regions of mouse development. Development 121: 3603–3613.

    External Resources

  32. Makarenkova, H.P., M. Ito, V. Govindarajan, S.C. Faber, L. Sun, G. McMahon, P.A. Overbeek, R.A. Lang (2000) FGF 10 is an inducer and Pax6 a competence factor for lacrimal gland development. Development 127: 2563–2572.
  33. Mansouri, A., G. Goudreau, P. Gruss (1999) Pax genes and their role in organogenesis. Cancer Res 59(suppl): 1707s–1710s.
  34. Meech, R., P. Kallunki, G.M. Edelman, F.S. Jones (1999) A binding site for homeodomain and Pax proteins is necessary for L1 cell adhesion molecule gene adhesion by Pax-6 and bone morphogenetic proteins. Proc Natl Acad Sci USA 96: 2420–2425.
  35. Melnick, M., T. Jaskoll (2000) Mouse submandibular gland morphogenesis: A paradigm for embryonic signal processing. Crit Rev Oral Biol Med 11: 199–215.

    External Resources

  36. Miller, D.L., S. Ortega, O. Bashayan, R. Basch, C. Basilico (2000) Compensation by fibroblast growth factor 1 (FGF1) does not account for the mild phenotypic defects observed in FGF2 null mice. Mol Cell Biol 20: 2260–2268.
  37. Montero, A., Y. Okada, M. Tomita, M. Ito, H. Tsurukami, T. Nakamura, T. Doetschman, J.D. Coffin, M.M. Hurley (2000) Disruption of the fibroblast growth factor-2 gene results in decreased bone mass and bone formation. J Clin Invest 105: 1085–1093.
  38. Neubuser, A., H. Peters, R. Balling, G.R. Martin (1997) Antagonistic interactions between FGF and BMP signaling pathways: A mechanism for positioning the sites of tooth formation. Cell 90: 247–255.

    External Resources

  39. Noden, D.M. (1983) The role of the neural crest in patterning of avian cranial skeletal, connective, and muscle tissue. Dev Biol 96: 144–165.

    External Resources

  40. Noll, M. (1993) Evolution and role of Pax genes. Curr Opin Genet Dev 3: 595–605.

    External Resources

  41. Ohuchi, H., Y. Hori, M. Yamasaki, H. Harada, K. Sekine, S. Kato, N. Itoh (2000) FGF10 acts as a major ligand for FGF receptor 2 IIIb in mouse multi-organ development. Biochem Biophys Res Commun 277: 643–649.

    External Resources

  42. Ornitz, D.M., J. Xu, J.S. Colvin, D.G. McEwen, C.A. MacArthur, F. Coulier, G. Gao, M. Goldfarb (1996) Receptor specificity of the fibroblast growth factor family. J Biol Chem 271: 15292–15297.
  43. Orr-Urtreger, A., D. Givol, A. Yayon, Y. Yarden, P. Lonai (1991) Developmental expression of two murine fibroblast growth factor receptors, flg and bek. Development 113: 1419–1434.
  44. Peters, H., A. Neubuser, K. Kratochwil, R. Balling (1998) Pax9-deficient mice lack pharyngeal pouch derivatives and teeth and exhibit craniofacial and limb abnormalities. Genes Dev 12: 2735–2747.

    External Resources

  45. Peters, H., R. Balling (1999) Teeth. Where and how to make them. Trends Genet 15: 59–65.

    External Resources

  46. Pratt, T., T. Vitalis, N. Warren, J.M. Edgar, J.O. Mason, D.J. Price (2000) A role for Pax6 in the normal development of dorsal thalamus and its cortical connections. Development 127: 5167–5178.

    External Resources

  47. Schmahl, W., M. Knoedlseder, J. Favor, D. Davidson (1993) Defects of neuronal migration and the pathogenesis of cortical malformations are associated with Small eye (Sey) in the mouse, a point mutation at the Pax-6-locus. Acta Neuropathol 86: 126–135.
  48. St-Onge, L., B. Sosa-Pineda, K. Chowdhury, A. Mansouri, P. Gruss (1997) Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas. Nature 387: 406–409.
  49. Stoykova, A., M. Gotz, P. Gruss, J. Price (1997) Pax6-dependent regulation of adhesive patterning, R-cadherin expression and boundary formation in developing forebrain. Development 124: 3765–3777.
  50. Theiler, K. (1989) The House Mouse. New York, Springer.
  51. Trumpp, A., M.J. Depew, J.L.R. Rubenstein, J.M. Bishop, G.R. Martin (1999) Cre-mediated gene inactivation demonstrates that FGF8 is required for cell survival and patterning of the first branchial arch. Genes Dev 13: 3136–3148.
  52. Tucker, A.S., G. Yamada, M. Grigoriou, V. Pachnis, P.T. Sharpe (1999) Fgf-8 determines rostral-caudal polarity in the first branchial arch. Development 126: 51–61.

    External Resources

  53. Wang, Y.-H., B. Rutherford, W.B. Upholt, M. Mina (1999) Effects of BMP-7 on mouse tooth mesenchyme and chick mandibular mesenchyme. Dev Dyn 216: 320–335.
  54. Warburton, D., M. Schwarz, D. Tefft, G. Flores-Delgado, K.D. Anderson, W.V. Cardoso (2000) The molecular basis of lung morphogenesis. Mech Dev 92: 55–81.
  55. Weaver, M., N.R. Dunn, B.L.M. Hogan (2000) Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis. Development 127: 2695–2704.
  56. Weaver, M., J.M. Yingling, N.R. Dunn, S. Bellusci, B.L.M. Hogan (1999) Bmp signaling regulates proximal-distal differentiation of endoderm in mouse lung development. Development 126: 4005–4015.

    External Resources

  57. Weinstein, M., X. Xu, K. Ohyama, C.X. Deng (1998) FGFR-3 and FGFR-4 function cooperatively to direct alveogenesis in the murine lung. Development 125:3615–3623.

    External Resources

  58. Wessells, N.K. (1977) Tissue Interactions and Development. Menlo Park, Benjamin/Cummings.
  59. Xu, X., C. Li, K. Takahashi, H.C. Slavkin, L. Shum, C.-X. Deng (1999) Murine fibroblast growth factor receptor 1α isoforms mediate node regression and are essential for posterior mesoderm development. Dev Biol 208: 293–306.

    External Resources

  60. Xu, X., M. Weinstein, C. Li, M. Naski, R.I. Cohen, D.M. Ornitz, P. Leder, C. Deng (1998) Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction. Development 125: 753–765.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50