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JOURNAL ARTICLES
Conserved regulation of mesenchymal gene expression by Fgf-8 in face and limb development
A.S. Tucker, A. Al Khamis, C.A. Ferguson, I. Bach, M.G. Rosenfeld, P.T. Sharpe
Development 1999 126: 221-228;

Summary

Clim-2 (NLI, Lbd1) is one of two related mouse proteins that interact with Lim-domain homeoproteins. In the mouse, embryonic expression of Clim-2 is particularly pronounced in facial ectomesenchyme and limb bud mesenchyme in association with Lim genes, Lhx-6 and Lmx-1 respectively. We show that in common with both these Lim genes, Clim-2 expression is regulated by signals from overlying epithelium. In both the developing face and the limb buds we identify Fgf-8 as the likely candidate signalling molecule that regulates Clim-2 expression. We show that in the mandibular arch, as in the limb, Fgf-8 functions in combination with CD44, a cell surface binding protein, and that blocking CD44 binding results in inhibition of Fgf8-induced expression of Clim-2 and Lhx-6. Regulation of gene expression by Fgf8 in association with CD44 is thus conserved between limb and mandibular arch development.

Reference

    1. Åberg T.,
    2. Wozney J.,
    3. Thesleff I.
    (1997) Expression patterns of bone morphogenetic proteins (Bmps) in the developing mouse tooth suggest roles in morphogenesis and cell differentiation. Dev. Dyn 210, 383–396
    OpenUrlCrossRefPubMedWeb of Science
    1. Agulnick A. D.,
    2. Taira M.,
    3. Breen J. J.,
    4. Tanaka T.,
    5. Dawid I. B.,
    6. Westphal H.
    (1996) Interactions of the Lim-domain-binding factor Ldb1 with Lim homeodomain proteins. Nature 384, 270–272
    OpenUrlCrossRefPubMedWeb of Science
    1. Bach I.,
    2. Carriere C.,
    3. Ostendorff H. P.,
    4. Andersen B.,
    5. Rosenfeld M.G.
    (1997) A family of LIM domain-associated cofactors confer transcriptional synergism between LIM and Otx homeodomain proteins. Genes Dev 11, 1370–1380
    OpenUrlAbstract/FREE Full Text
    1. Breen J. J.,
    2. Agulnick A. D.,
    3. Westphal S.,
    4. Dawid I. B.
    (1998) Interactions between LIM domains and the LIM domain-binding protein Ldb1. J. Biol. Chem 273, 4712–4717
    OpenUrlAbstract/FREE Full Text
    1. Brown J. M.,
    2. Wedden S. E.,
    3. Millburn G. H.,
    4. Robson L. G.,
    5. Hill R. E.,
    6. Davidson D. R.,
    7. Tickle C.
    (1993) Experimental-analysis of the control of expression of the homeobox-gene Msx-1 in the developing limb and face. Development 119, 41–48
    OpenUrlAbstract
    1. Buckland R. A.,
    2. Collinson J. M.,
    3. Graham E.,
    4. Davidson D. R.,
    5. Hill R. E.
    (1998) Antagonistic effects of FGF4 on BMP induction of apoptosis and chondrogenesis in the chick limb bud. Mech. Dev 71, 143–150
    OpenUrlCrossRefPubMedWeb of Science
    1. Bulfone A.,
    2. Kim H. J.,
    3. Puelles L.,
    4. Porteus M. H.,
    5. Grippo J. F.,
    6. Rubenstein J. L. R.
    (1993) The mouse Dlx-2 (Tes-1) gene is expressed in spatially restricted domains of the forebrain, face and limbs in midgestation mouse embryos. Mech. Dev 40, 129–140
    OpenUrlCrossRefPubMedWeb of Science
    1. Celli G.,
    2. LaRochelle W. J.,
    3. Mackem S.,
    4. Sharp R.,
    5. 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
    OpenUrlAbstract
    1. Chen Y. P.,
    2. Bei M.,
    3. Woo I.,
    4. Satokata I.,
    5. Maas R.
    (1996) Msx1 controls inductive signaling in mammalian tooth morphogenesis. Development 122, 3035–3044
    OpenUrlAbstract
    1. Chen Y. P.,
    2. Satokata I.,
    3. Heaney S.,
    4. Woo I.,
    5. Maas R.
    (1997) Control of limb bud pattern formation and apoptosis by mouse Msx genes. Dev. Biol 186, 228–.
    OpenUrl
    1. Crossley P. H.,
    2. Martin G. R.
    (1995) The mouse Fgf8 gene encodes a family of polypeptides and is expressed in regions that direct outgrowth and patterning in the developing embryo. Development 121, 439–451
    OpenUrlAbstract
    1. Crossley P. H.,
    2. Martinez S.,
    3. Martin G. R.
    (1996) Midbrain development induced by Fgf8 in the chick-embryo. Nature 380, 66–68
    OpenUrlCrossRefPubMed
    1. Cygan J. A.,
    2. Johnson R. L.,
    3. McMahon A. P.
    (1997) Novel regulatory interactions revealed by studies of murine limb pattern in Wnt-7a and En-1 mutants. Development 124, 5021–5032
    OpenUrlAbstract
    1. Dawid I. B.,
    2. Breen J. J.,
    3. Toyama R.
    (1998) LIM domains: multiple roles as adapters and functional modifiers in protein interactions. Trends Genet 14, 156–162
    OpenUrlCrossRefPubMedWeb of Science
    1. Ferrari D.,
    2. Sumoy L.,
    3. Gannon J.,
    4. Sun H. L.,
    5. Brown A. M. C.,
    6. Upholt W. B.,
    7. Kosher R. A.
    (1995) The expression pattern of the distal-less homeobox-containing gene Dlx-5 in the developing chick limb bud suggests its involvement in apical ectodermal ridge activity, pattern-formation, and cartilage differentiation. Mech. Dev 52, 257–264
    OpenUrlCrossRefPubMedWeb of Science
    1. Francis P. H.,
    2. Richardson M. K.,
    3. Brickell P. M.,
    4. Tickle C.
    (1994) Bone morphogenetic proteins and a signaling pathway that controls patterning in the developing chick limb. Development 120, 209–218
    OpenUrlAbstract
    1. Grigoriou M.,
    2. Tucker A. S.,
    3. Sharpe P. T.,
    4. Pachnis V.
    (1998) Expression of Lhx-6 and Lhx-7, a novel subfamily of Lim homeodomain genes, suggests a role in mammalian head development. Development 125, 2063–2074
    OpenUrlAbstract
    1. Hardcastle Z.,
    2. Rong M.,
    3. Chi-chung H.,
    4. Sharpe P. T.
    (1998) The Shh signalling pathway in tooth development: defects in Gli2 and Gli3 mutants. Development 125, 2803–2811
    OpenUrlAbstract
    1. Heikinheimo M.,
    2. Lawshe A.,
    3. Shackleton G. M.,
    4. Wilson D. B.,
    5. MacArthur C. A.
    (1994) Fgf-8 expression in the post-gastrulation mouse suggests roles in the developing face, limbs and central nervous system. Mech. Dev 48, 129–138
    OpenUrlCrossRefPubMedWeb of Science
    1. Jernvall J.,
    2. Kettunen P.,
    3. Karavanova I.,
    4. Martin L. B.,
    5. Thesleff I.
    (1994) Evidence for the role of the Enamel Knot as a control center in mammalian tooth cusp formation—Nondividing cells express growth-stimulating Fgf-4 gene. Int. J. Dev. Biol 38, 463–469
    OpenUrlPubMedWeb of Science
    1. Jones C. M.,
    2. Lyons K. M.,
    3. Hogan B. L. M.
    (1991) Involvement of Bone-Morphogenetic Protein-4 (Bmp-4) and Vgr-1 in morphogenesis and neurogenesis in the mouse. Development 111, 531–.
    OpenUrlAbstract
    1. Jurata L. W.,
    2. Kenny D. A.,
    3. Gill G. N.
    (1996) Nuclear Lim Interactor, a rhombotin and Lim homeodomain interacting protein, is expressed early in neuronal development. Proc. Nat. Acad. Sci. USA 93, 11693–11698
    OpenUrlAbstract/FREE Full Text
    1. Kettunen P.,
    2. Thesleff I.
    (1998) Expression and function of FGFs-4,-8, and-9 suggest functional redundancy and repetitive use as epithelial signals during tooth morphogenesis. Dev. Dyn 211, 256–268
    OpenUrlCrossRefPubMedWeb of Science
    1. Kitanaka J. I.,
    2. Takemura M.,
    3. Matsumoto K.,
    4. Mori T.,
    5. Wanaka A.
    (1998) Structure and chromosomal localization of a murine Lim/homeobox gene, Lhx-8. Genomics 49, 307–309
    OpenUrlCrossRefPubMedWeb of Science
    1. Koyama E.,
    2. Yamaai T.,
    3. Iseki S.,
    4. Ohuchi H.,
    5. Nohno T.,
    6. Yoshioka H.,
    7. Hayashi Y.,
    8. Leatherman J. L.,
    9. Golden E. B.,
    10. Noji S.,
    11. et al.
    (1996) Polarizing activity, sonic hedgehog, and tooth development in embryonic and postnatal mouse. Dev. Dyn 206, 59–72
    OpenUrlCrossRefPubMedWeb of Science
    1. Lyons K. M.,
    2. Pelton R. W.,
    3. Hogan B. L. M.
    (1990) Organogenesis and pattern-formation in the mouse—RNA distribution patterns suggest a role for Bone Morphogenetic Protein-2a (Bmp-2a). Development 109, 833–.
    OpenUrlAbstract/FREE Full Text
    1. Martin G. R.
    (1998) The roles of FGFs in the early development of vertebrate limbs. Genes Dev 12, 1571–1586
    OpenUrlFREE Full Text
    1. Meyers E. N.,
    2. Lewandoski M.,
    3. Martin G. R.
    (1998) Generation of an Fgf-8 mutant allelic series using a single targeted mouse line carrying Cre and Flp recombinase recognition sites. Nature Genet 18, 136–141
    OpenUrlCrossRefPubMedWeb of Science
    1. Morcillo P.,
    2. Rosen C.,
    3. Baylies M. K.,
    4. Dorsett D.
    (1997) Chip, a widely expressed chromosomal protein required for segmentation and activity of a remote wing margin enhancer in Drosophila. Genes Dev 11, 2729–2740
    OpenUrlAbstract/FREE Full Text
    1. Neubuser A.,
    2. Peters H.,
    3. Balling R.,
    4. Martin G. R.
    (1997) Antagonistic interactions between FGF and BMP signaling pathways: A mechanism for positioning the sites of tooth formation. Cell 90, 247–255
    OpenUrlCrossRefPubMedWeb of Science
    1. Ponta H.,
    2. Wainwright D.,
    3. Herrlich P.
    (1998) The CD44 protein family. Int. J. Biochem. Cell Biol 30, 299–305
    OpenUrlCrossRefPubMedWeb of Science
    1. Pownall M. E.,
    2. Tucker A. S.,
    3. Slack J. M. W.,
    4. Isaacs H. V.
    (1996) eFGF, Xcad3 and Hox genes form a molecular pathway that establishes the anteroposterior axis in Xenopus. Development 122, 3881–3892
    OpenUrlAbstract
    1. Qiu M. S.,
    2. Bulfone A.,
    3. Martinez S.,
    4. Meneses J. J.,
    5. Shimamura K.,
    6. Pedersen R. A.,
    7. Rubenstein J. L. R.
    (1995) Null mutation of Dlx-2 results in abnormal morphogenesis of proximal first and 2nd branchial arch derivatives and abnormal differentiation in the forebrain. Genes Dev 9, 2523–2538
    OpenUrlAbstract/FREE Full Text
    1. Rahmanian M.,
    2. Pertoft H.,
    3. Kanda S.,
    4. Christofferson R.,
    5. Claesson Welsh L.,
    6. Heldin P.
    (1997) Hyaluronan oligosaccharides induce tube formation of a brain endothelial cell line in vitro. Exp. Cell Res 237, 223–230
    OpenUrlCrossRefPubMedWeb of Science
    1. Riddle R. D.,
    2. Ensini M.,
    3. Nelson C.,
    4. Tsuchida T.,
    5. Jessell T. M.,
    6. Tabin C.
    (1995) Induction of the Lim homeobox gene Lmx1 by Wnt7a establishes dorsoventral pattern in the vertebrate limb. Cell 83, 631–640
    OpenUrlCrossRefPubMedWeb of Science
    1. Saxen L.
    (1966) The effect of Tetracyclin on osteogenesis in vitro. J. exp. Zool 162, 269–294
    OpenUrlCrossRef
    1. Sheng H. Z.,
    2. Zhadanov A. B.,
    3. Mosinger B. Jr,
    4. Fujii T.,
    5. Bertuzzi S.,
    6. Grinberg A.,
    7. Lee E. J.,
    8. Huang S.-P.,
    9. Mahon K. A.,
    10. Westphal H.
    (1996) Specification of pituitary cell lineages by the Lim homeobox gene Lhx-3. Science 272, 1004–1007
    OpenUrlAbstract
    1. Sherman L.,
    2. Wainwright D.,
    3. Ponta H.,
    4. Herrlich P.
    (1998) A splicevariant of CD44 expressed in the apical ectodermal ridge presents to limb mesenchyme and is required for limb outgrowth. Genes Dev 12, 1058–1071
    OpenUrlAbstract/FREE Full Text
    1. Skelton T. P.,
    2. Zeng C. X.,
    3. Nocks A.,
    4. Stamenkovic I.
    (1998) Glycosylation provides both stimulatory and inhibitory effects on cell surface and soluble CD44 binding to hyaluronan. J. Cell Biol 140, 431–446
    OpenUrlAbstract/FREE Full Text
    1. Toyama R.,
    2. Kobayashi M.,
    3. Tomita T.,
    4. Dawid I. B.
    (1998) Expression of LIM-domain binding protein (ldb) genes during zebrafish embryogenesis. Mech. Dev 71, 197–200
    OpenUrlCrossRefPubMedWeb of Science
    1. Treier M.,
    2. Gleiberman A. S.,
    3. O'Connell S. M.,
    4. Szeto D. P.,
    5. McMahon J. A.,
    6. McMahon A. P.,
    7. Rosenfeld M. G.
    (1998) Multistep signaling requirements for pituitary organogenesis in vivo. Genes Dev 12, 1691–1704
    OpenUrlAbstract/FREE Full Text
    1. Trowel O. A.
    (1959) The culture of mature organs in a synthetic medium. Exp. Cell Res 16, 118–147
    OpenUrlCrossRefPubMedWeb of Science
    1. Tucker A. S.,
    2. Al Khamis A.,
    3. Sharpe P. T.
    (1998) Interactions between Bmp-4 and Msx-1 act to restrict gene expression to odontogenic mesenchyme. Dev. Dyn 212, 533–539
    OpenUrlCrossRefPubMedWeb of Science
    1. Tucker A. S.,
    2. Yamada G.,
    3. Grigoriou M.,
    4. Pachnis V.,
    5. Sharpe P. T.
    (1999) Fgf-8 determines rostral-caudal polarity in the first branchial arch. Development 126, 11–51
    OpenUrlCrossRef
    1. Vaahtokari A.,
    2. Åberg T.,
    3. Jernvall J.,
    4. Keranen S.,
    5. Thesleff I.
    (1996) The enamel knot as a signaling center in the developing mouse tooth. Mech. Dev 54, 39–43
    OpenUrlCrossRefPubMedWeb of Science
    1. Vogel A.,
    2. Rodriguez C.,
    3. Warnken W.,
    4. Izpisua Belmonte J. C.
    (1995) Dorsal cell fate specified by chick Lmx-1 during vertebrate limb development. Nature 378, 716–720
    OpenUrlCrossRefPubMed
    1. Wanaka A.,
    2. Matsumoto K.,
    3. Kashihara Y.,
    4. Furuyama T.,
    5. Tanaka T.,
    6. Mori T.,
    7. Tanno Y.,
    8. Yokoya S.,
    9. Kitanaka J.,
    10. Takemura M.,
    11. et al.
    (1997) LIM-homeodomain gene family in neural development. Dev. Neurosci 19, 97–100
    OpenUrlPubMedWeb of Science
    1. Wheatley S. C.,
    2. Isacke C. M.,
    3. Crossley P. H.
    (1993) Restricted expression of the hyaluronan receptor, CD44, during postimplantation mouse embryogenesis suggests key roles in tissue formation and patterning. Development 119, 295–306
    OpenUrlAbstract
    1. Yu Q.,
    2. Grammatikakis N.,
    3. Toole B. P.
    (1996) Expression of multiple CD44 isoforms in the apical ectodermal ridge of the embryonic mouse limb. Dev. Dyn 207, 204–214
    OpenUrlCrossRefPubMedWeb of Science
    1. Yu Q.,
    2. Toole B. P.
    (1997) Common pattern of CD44 isoforms expressed in morphogenetically active epithelia. Dev. Dyn 208, 1–10
    OpenUrlCrossRefPubMedWeb of Science
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JOURNAL ARTICLES
Conserved regulation of mesenchymal gene expression by Fgf-8 in face and limb development
A.S. Tucker, A. Al Khamis, C.A. Ferguson, I. Bach, M.G. Rosenfeld, P.T. Sharpe
Development 1999 126: 221-228;
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