Advertisement
JOURNAL ARTICLES
The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor
H. Ohuchi, T. Nakagawa, A. Yamamoto, A. Araga, T. Ohata, Y. Ishimaru, H. Yoshioka, T. Kuwana, T. Nohno, M. Yamasaki, N. Itoh, S. Noji
Development 1997 124: 2235-2244;

Summary

Vertebrate limb formation has been known to be initiated by a factor(s) secreted from the lateral plate mesoderm. In this report, we provide evidence that a member of the fibroblast growth factor (FGF) family, FGF10, emanates from the prospective limb mesoderm to serve as an endogenous initiator for limb bud formation. Fgf10 expression in the prospective limb mesenchyme precedes Fgf8 expression in the nascent apical ectoderm. Ectopic application of FGF10 to the chick embryonic flank can induce Fgf8 expression in the adjacent ectoderm, resulting in the formation of an additional complete limb. Expression of Fgf10 persists in the mesenchyme of the established limb bud and appears to interact with Fgf8 in the apical ectoderm and Sonic hedgehog in the zone of polarizing activity. These results suggest that FGF10 is a key mesenchymal factor involved in the initial budding as well as the continuous outgrowth of vertebrate limbs.

REFERENCES

    1. Burke A. C.,
    2. Nelson C. E.,
    3. Morgan B. A.,
    4. Tabin C.
    (1995) Hox genes and the evolution of vertebrate axial morphology. Development 121, 333–346
    OpenUrlAbstract
    1. Cohn M. J.,
    2. Izpisúa-Belmonte J. C.,
    3. Abud H.,
    4. Heath J. K.,
    5. Tickle C.
    (1995) Fibroblast growth factors induce additional limb development from the flank of chick embryos. Cell 80, 739–746
    OpenUrlCrossRefPubMedWeb of Science
    1. Cohn M. J.,
    2. Tickle C.
    (1996) Limbs: a model for pattern formation within the vertebrate body plan. Trends in Genetics 12, 253–257
    OpenUrlCrossRefPubMedWeb of Science
    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. Minowada G.,
    3. MacArthur C. A.,
    4. Martin G. R.
    (1996) Roles for FGF8 in the induction, initiation, and maintenance of chick limb development. Cell 84, 127–136
    OpenUrlCrossRefPubMedWeb of Science
    1. Dealy C. N.,
    2. Kosher R. A.
    (1996) IGF-I and insulin in the acquisition of limb-forming ability by the embryonic lateral plate. Dev. Biol 177, 291–299
    OpenUrlCrossRefPubMed
    1. Dhouailly D.,
    2. Kieny M.
    (1972) The capacity of the flank somatic mesoderm of early bird embryos to participate in limb development. Dev. Biol 28, 162–175
    OpenUrlCrossRefPubMedWeb of Science
    1. Fallon J. F.,
    2. Lopez A.,
    3. Ros M. A.,
    4. Savage M. P.,
    5. Olwin B. B.,
    6. Simandl B. K.
    (1994) FGF-2: Apical ectodermal ridge growth signal for chick limb development. Science 264, 104–107
    OpenUrlAbstract/FREE Full Text
    1. Fekete D. M.,
    2. Cepko C. L.
    (1993) Replication-competent retroviral vectors encoding alkaline phosphatase reveal spatial restriction of viral gene expression/transduction in the chick embryo. Mol. Cell. Biol 13, 2604–2613
    OpenUrlAbstract/FREE Full Text
    1. Frohman M. A.,
    2. Dush M. K.,
    3. Martin G. R.
    (1988) Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc. Natl. Acad. Sci. USA 85, 8998–9002
    OpenUrlAbstract/FREE Full Text
    1. Gibson-Brown J. J.,
    2. Agulnik S. I.,
    3. Chapman D. L.,
    4. Alexiou M.,
    5. Garvey N.,
    6. Silver L. M.,
    7. Papaioannou V. E.
    (1996) Evidence of a role for T-box genes in the evolution of limb morphogenesis and the specification of forelimb/hindlimb identity. Mech. Dev 56, 93–101
    OpenUrlCrossRefPubMedWeb of Science
    1. Grieshammer U.,
    2. Minowada G.,
    3. Pisenti J. M.,
    4. Abbott U. K.,
    5. Martin G. R.
    (1996) The chick limbless mutation causes abnormalities in limb bud dorsal-ventral patterning: implications for the mechanism of apical ridge formation. Development 122, 3851–3861
    OpenUrlAbstract
    1. Hamburger V.,
    2. Hamilton H. L.
    (1951) A series of normal stages in the development of the chick embryo. J. Morphol 94, 257–265
    OpenUrlCrossRef
    1. Heymann S.,
    2. Koudrova M.,
    3. Arnold H. H.,
    4. Köster M.,
    5. Braun T.
    (1996) Regulation and function of SF/HGF during migration of limb muscle precursor cells in chicken. Dev. Biol 180, 566–578
    OpenUrlCrossRefPubMed
    1. Hughes S. H.,
    2. Greenhouse J. J.,
    3. Petropoulos C. J.,
    4. Sutrave P.
    (1987) Adaptor plasmids simplify the insertion of foreign DNA into helper-independent retroviral vectors. J. Virol 61, 3004–3012
    OpenUrlAbstract/FREE Full Text
    1. Kuwana T.,
    2. Hashimoto K.,
    3. Nakanishi A.,
    4. Yasuda Y.,
    5. Tajima A.,
    6. Naito M.
    (1996) Long-term culture of avian embryonic cells in vitro. Int. J. Dev. Biol 40, 1061–1064
    OpenUrlPubMedWeb of Science
    1. Laufer E.,
    2. Nelson C. E.,
    3. Johnson R. L.,
    4. Morgan B. A.,
    5. Tabin C.
    (1994) Sonic hedgehog and Fgf-4 act through a signaling cascade and feedback loop to integrate growth and patterning of the developing limb bud. Cell 79, 993–1003
    OpenUrlCrossRefPubMedWeb of Science
    1. Loomis C. A.,
    2. Harris E.,
    3. Michaud J.,
    4. Wurst W.,
    5. Hanks M.,
    6. Joyner A. L.
    (1996) The mouse Engrailed-1 gene and ventral limb patterning. Nature 382, 360–363
    OpenUrlCrossRefPubMedWeb of Science
    1. MacArthur C. A.,
    2. Lawshe A.,
    3. Xu J.,
    4. Santos-Ocampo S.,
    5. Heikinheimo M.,
    6. Chellaiah A. T.,
    7. Ornitz D. M.
    (1995) FGF-8 isoforms activate receptor splice forms that are expressed in mesenchymal regions of mouse development. Development 121, 3603–3613
    OpenUrlAbstract
    1. Mahmood R.,
    2. Bresnick J.,
    3. Hornbruch A.,
    4. Mahony C.,
    5. Morton N.,
    6. Colquhoun K.,
    7. Martin P.,
    8. Lumsden A.,
    9. Dickson C.,
    10. Mason I.
    (1995) A role for FGF-8 in the initiation and maintenance of vertebrate limb bud outgrowth. Curr. Biol 5, 797–806
    OpenUrlCrossRefPubMedWeb of Science
    1. Mason I. J.,
    2. Fuller-Pace F.,
    3. Smith R.,
    4. Dickson C.
    (1994) FGF-7 (keratinocyte growth factor) expression during mouse development suggests roles in myogenesis, forebrain regionalisation and epithelial-mesenchymal interactions. Mech. Dev 45, 15–30
    OpenUrlCrossRefPubMedWeb of Science
    1. Niswander L.,
    2. Martin G. R.
    (1992) Fgf-4 expression during gastrulation, myogenesis, limb and tooth development in the mouse. Development 114, 755–768
    OpenUrlAbstract
    1. Niswander L.,
    2. Tickle C.,
    3. Vogel A.,
    4. Booth I.,
    5. Martin G. R.
    (1993) FGF-4 replaces the apical ectodermal ridge and directs outgrowth and patterning of the limb. Cell 75, 579–587
    OpenUrlCrossRefPubMedWeb of Science
    1. Niswander L.,
    2. Jeffrey S.,
    3. Martin G. R.,
    4. Tickle C.
    (1994) A positive feedback loop coordinates growth and patterning in the vertebrate limb. Nature 371, 609–612
    OpenUrlCrossRefPubMed
    1. Nohno T.,
    2. Kawakami Y.,
    3. Ohuchi H.,
    4. Fujiwara A.,
    5. Yoshioka H.,
    6. Noji S.
    (1995) Involvement of the Sonic hedgehog gene in chick feather formation. Biochem. Biophys. Res. Commun 206, 33–39
    OpenUrlCrossRefPubMedWeb of Science
    1. Noramly S.,
    2. Pisenti J.,
    3. Abbott U.,
    4. Morgan B.
    (1996) Gene expression in the limbless mutant: Polarized gene expression in the absence of Shh and an AER. Dev. Biol 179, 339–346
    OpenUrlCrossRefPubMedWeb of Science
    1. Ohuchi H.,
    2. Yoshioka H.,
    3. Tanaka A.,
    4. Kawakami Y.,
    5. Nohno T.,
    6. Noji S.
    (1994) Involvement of androgen-induced growth factor (FGF-8) gene in mouse embryogenesis and morphogenesis. Biochem. Biophys. Res. Commun 204, 882–888
    OpenUrlCrossRefPubMedWeb of Science
    1. Ohuchi H.,
    2. Nakagawa T.,
    3. Yamauchi M.,
    4. Ohata T.,
    5. Yoshioka H.,
    6. Kuwana T.,
    7. Mima T.,
    8. Mikawa T.,
    9. Nohno T.,
    10. Noji S.
    (1995) An additional limb can be induced from the flank of the chick embryo by FGF4. Biochem. Biophys. Res. Commun 209, 809–816
    OpenUrlCrossRefPubMedWeb of Science
    1. Ohuchi H.,
    2. Shibusawa M.,
    3. Nakagawa T.,
    4. Ohata T.,
    5. Yoshioka H.,
    6. Hirai Y.,
    7. Nohno T.,
    8. Noji S.,
    9. Kondo N.
    (1997) A chick wingless mutation causes abnormality in maintenance of Fgf8 expression in the wing apical ridge, resulting in loss of the dorsoventral boundary. Mech. Dev 62, 3–13
    OpenUrlCrossRefPubMed
    1. Ornitz D. M.,
    2. Xu J.,
    3. Colvin J. S.,
    4. McEwen D. G.,
    5. MacArthur C. A.,
    6. Coulier F.,
    7. Gao G.,
    8. Goldfarb M.
    (1996) Receptor specificity of the fibroblast growth factor family. J. Biol. Chem 271, 15292–15297
    OpenUrlAbstract/FREE Full Text
    1. Orr-Urtreger A.,
    2. Bedford M. T.,
    3. Burakova T.,
    4. Arman E.,
    5. Zimmer Y.,
    6. Yayon A.,
    7. Givol D.,
    8. Lonai P.
    (1993) Developmental localization of the splicing alternatives of fibroblast growth factor receptor-2 (FGFR2). Dev. Biol 158, 475–486
    OpenUrlCrossRefPubMedWeb of Science
    1. Pinot M.
    (1970) Le rôle du mesoderme somitique dans la morphogeneseprecoce des membres de l'embryon de Poulet. J. Embryol. Exp. Morph 23, 109–151
    OpenUrlPubMed
    1. Riddle R. D.,
    2. Johnson R. L.,
    3. Laufer E.,
    4. Tabin C.
    (1993) Sonic hedgehog mediates the polarizing activity of the ZPA. Cell 75, 1401–1416
    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. Ros M. A.,
    2. Lopez-Martinez A.,
    3. Simandl B. K.,
    4. Rodriguez C.,
    5. Izpisúa-Belmonte J. C.,
    6. Dahn R.,
    7. Fallon J. F.
    (1996) The limb field mesoderm determines initial limb bud anteroposterior asymmetry and budding independent of sonic hedgehog or apical ectodermal gene expressions. Development 122, 2319–2330
    OpenUrlAbstract
    1. Rowe D. A.,
    2. Fallon J. F.
    (1981) The effect of removing posterior apical ectodermal ridge of the chick wing and leg on pattern formation. J. Embryol. Exp. Morph 65, 309–325
    1. Sasaki H.,
    2. Hogan B. L.
    (1993) Differential expression of multiple fork head related genes during gastrulation and axial pattern formation in the mouse embryo. Development 118, 47–59
    OpenUrlAbstract
    1. Saunders J. W., Jr
    (1948) The proximo-distal sequence of origin of the parts of the chick wing and the role of the ectoderm. J. Exp. Zool 108, 363–403
    OpenUrlCrossRefPubMedWeb of Science
    1. Saunders J. W., Jr.,
    2. Gasseling M. T.
    (1963) Trans-filter propagation of apical ectoderm maintenance factor in the chick embryo wing bud. Dev. Biol 7, 64–78
    OpenUrlCrossRefPubMedWeb of Science
    1. Saunders J. W., Jr.,
    2. Reuss C.
    (1974) Inductive and axial properties of prospective wing-bud mesoderm in the chick embryo. Dev. Biol 38, 41–50
    OpenUrlCrossRefPubMed
    1. Savage M. P.,
    2. Hart C. E.,
    3. Riley B. B.,
    4. Sasse J.,
    5. Olwin B. B.,
    6. Fallon J. F.
    (1993) Distribution of FGF-2 suggests it has a role in chick limb bud growth. Dev. Dyn 198, 159–170
    OpenUrlCrossRefPubMedWeb of Science
    1. Searls R. L.,
    2. Janners M. Y.
    (1971) The initiation of limb bud outgrowth in the embryonic chick. Dev. Biol 24, 198–213
    OpenUrlCrossRefPubMedWeb of Science
    1. Slack J. M. W.
    (1995) Growth factor lends a hand. Nature 374, 217–218
    OpenUrlCrossRefPubMed
    1. Stephens T. D.,
    2. Beier R. L. W.,
    3. Bringhurst D. C.,
    4. Hiatt S. R.,
    5. Prestridge M.,
    6. Pugmire D. E.,
    7. Willis H. J.
    (1989) Limbness in the early chick embryo lateral plate. Dev. Biol 133, 1–7
    OpenUrlCrossRefPubMed
    1. Streck R. D.,
    2. Wood T. L.,
    3. Hsu M.,
    4. Pintar J. E.
    (1992) Insulin-like growth factor I and II and insulin-like growth factor binding protein-2 RNAs are expressed in adjacent tissues within rat embryonic and fetal limbs. Dev. Biol 151, 586–596
    OpenUrlCrossRefPubMed
    1. Summerbell D.
    (1974) A quantitative analysis of the effect of excision of the AER from the chick limb-bud. J. Embryol. Exp. Morph 32, 651–660
    OpenUrlPubMedWeb of Science
    1. Thery C.,
    2. Sharpe M. J.,
    3. Batley S. J.,
    4. Stern C. D.,
    5. Gherardi E.
    (1995) Expression of HGF/SF, HGF1/MSP, and c-met suggests new functions during early chick development. Develop. Genet 17, 90–101
    OpenUrlCrossRefPubMedWeb of Science
    1. Vogel A.,
    2. Rodriguez C.,
    3. Warnken W.,
    4. Izpisúa-Belmonte J. C.
    (1995) Chick Lmx-1 specifies dorsal cells fate during vertebrate limb development. Nature 378, 716–720
    OpenUrlCrossRefPubMed
    1. Vogel A.,
    2. Rodriguez C.,
    3. Izpisúa-Belmonte J.
    (1996) Involvement of FGF-8 in initiation, outgrowth and patterning of the vertebrate limb. Development 122, 1737–1750
    OpenUrlAbstract
    1. Yamasaki M.,
    2. Miyake A.,
    3. Tagashira S.,
    4. Itoh N.
    (1996) Structure and expression of the rat mRNA encoding a novel member of the fibroblast growth factor family. J. Biol. Chem 271, 15918–15921
    OpenUrlAbstract/FREE Full Text
    1. Yang Y.,
    2. Niswander L.
    (1995) Interaction between the signaling molecules WNT7a and SHH during vertebrate limb development: Dorsal signals regulate anteroposterior patterning. Cell 80, 939–947
    OpenUrlCrossRefPubMedWeb of Science
    1. Zwilling E.,
    2. Hansborough L.
    (1956) Interaction between limb bud ectoderm and mesoderm in the chick embryo. III. Experiments with polydactylous limbs. J. Exp. Zool 132, 219–239
    OpenUrlCrossRefWeb of Science
Back to top

 Download PDF

Email
JOURNAL ARTICLES
The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor
H. Ohuchi, T. Nakagawa, A. Yamamoto, A. Araga, T. Ohata, Y. Ishimaru, H. Yoshioka, T. Kuwana, T. Nohno, M. Yamasaki, N. Itoh, S. Noji
Development 1997 124: 2235-2244;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Alerts

Article navigation

Other journals from The Company of Biologists

Advertisement

A new society for regenerative biologists

Kenneth Poss and Elly Tanaka announce the launch of the International Society for Regenerative Biology (ISRB), which will promote research and education in the field of regenerative biology.

Upcoming special issue: call for papers

The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022

The special issue welcomes Review articles as well as Research articles, and will be widely promoted online and at key global conferences.

An interview with Cagney Coomer

Over a virtual chat, we spoke to Cagney Coomer about her experiences in the lab, the classroom and the community centre, and why she thinks outreach and role models are vital to science.

Development presents...

Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Here, Michèle Romanos talks about her new preprint, which mixes experimentation in quail embryos and computational modelling to understand how heterogeneity in a tissue influences cell rate.

Save your spot at our next session:

10 March
Time: 9:00 (GMT)
Chaired by: Thomas Lecuit

Join our mailing list to receive news and updates on the series.