Expression of chicken fibroblast growth factor homologous factor (FHF)-1 and of differentially spliced isoforms of FHF-2 during development and involvement of FHF-2 in chicken limb development

Development ◽  
1999 ◽  
Vol 126 (2) ◽  
pp. 409-421
Author(s):  
I. Munoz-Sanjuan ◽  
B.K. Simandl ◽  
J.F. Fallon ◽  
J. Nathans
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Neural Tube ◽  
Limb Development ◽  
Limb Bud ◽  
Fibroblast Growth ◽  
Limb Buds ◽  
Adjacent Structures ◽  
Morphological Defects ◽  
Zone Of Polarizing Activity

Members of the fibroblast growth factor (FGF) family have been identified as signaling molecules in a variety of developmental processes, including important roles in limb bud initiation, growth and patterning. This paper reports the cloning and characterization of the chicken orthologues of fibroblast growth factor homologous factors-1 and −2 (cFHF-1/cFGF-12 and cFHF-2/cFGF-13, respectively). We also describe the identification of a novel, conserved isoform of FHF-2 in chickens and mammals. This isoform arises by alternative splicing of the first exon of the FHF-2 gene and is predicted to encode a polypeptide with a distinct amino-terminus. Whole-mount in situ hybridization reveals restricted domains of expression of cFHF-1 and cFHF-2 in the developing neural tube, peripheral sensory ganglia and limb buds, and shows that the two cFHF-2 transcript isoforms are present in non-overlapping spatial distributions in the neural tube and adjacent structures. In the developing limbs, cFHF-1 is confined to the posterior mesoderm in an area that encompasses the zone of polarizing activity and cFHF-2 is confined to the distal anterior mesoderm in a region that largely overlaps the progress zone. Ectopic cFHF-2 expression is induced adjacent to grafts of cells expressing Sonic Hedgehog and the zone of cFHF-2 expression is expanded in talpid2 embryos. In the absence of the apical ectodermal ridge or in wingless or limbless mutant embryos, expression of cFHF-1 and cFHF-2 is lost from the limb bud. A role for cFHF-2 in the patterning and growth of skeletal elements is implied by the observation that engraftment of developing limb buds with QT6 cells expressing a cFHF-2 isoform that is normally expressed in the limb leads to a variety of morphological defects. Finally, we show that a secreted version of cFHF-2 activates the expression of HoxD13, HoxD11, Fgf-4 and BMP-2 ectopically, consistent with cFHF-2 playing a role in anterior-posterior patterning of the limb.

Correlation of wing-leg identity in ectopic FGF-induced chimeric limbs with the differential expression of chick Tbx5 and Tbx4

Development ◽  
1998 ◽  
Vol 125 (1) ◽  
pp. 51-60 ◽  
Author(s):  
H. Ohuchi ◽  
J. Takeuchi ◽  
H. Yoshioka ◽  
Y. Ishimaru ◽  
K. Ogura ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Limb Bud ◽  
Chick Embryos ◽  
Fibroblast Growth ◽  
Limb Buds ◽  
Specific Position

It has been reported that members of the fibroblast growth factor (FGF) family can induce additional limb formation in the flank of chick embryos. The phenotype of the ectopic limb depends on the somite level at which it forms: limbs in the anterior flank resemble wings, whereas those in the posterior flank resemble legs. Ectopic limbs located in the mid-flank appear chimeric, possessing characteristics of both wings and legs; feather buds are present in the anterior halves with scales and claws in the posterior halves. To study the mechanisms underlying the chimerism of these additional limbs, we cloned chick Tbx5 and Tbx4 to use as forelimb and hindlimb markers and examined their expression patterns in FGF-induced limb buds. We found that Tbx5 and Tbx4 were differentially expressed in the anterior and posterior halves of additional limb buds in the mid-flank, respectively, consistent with the chimeric patterns of the integument. A boundary of Tbx5/Tbx4 exists in all ectopic limbs, indicating that the additional limbs are essentially chimeric, although the degree of chimerism is dependent on the position. The boundary of Tbx5/Tbx4 expression is not fixed at a specific position within the interlimb region, but dependent upon where FGF was applied. Since the ectopic expression patterns of Tbx5/Tbx4 in the additional limbs are closely correlated with the patterns of their chimeric phenotypes, it is likely that Tbx5 and Tbx4 expression in the limb bud is involved in determination of the forelimb and hindlimb identities, respectively, in vertebrates.

Retroviral expression of FGF-2 (bFGF) affects patterning in chick limb bud

Development ◽  
1993 ◽  
Vol 118 (1) ◽  
pp. 95-104 ◽  
Author(s):  
B.B. Riley ◽  
M.P. Savage ◽  
B.K. Simandl ◽  
B.B. Olwin ◽  
J.F. Fallon
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Limb Development ◽  
Limb Bud ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Donor Tissue ◽  
Wing Bud

To investigate the role of fibroblast growth factor-2 (basic fibroblast growth factor) in chick limb development, we constructed a replication-defective spleen necrosis virus to ectopically express fibroblast growth factor-2 in stage 20–22 chick limb bud. Because infecting cells in vivo proved to be inefficient, limb bud cells were dissociated, infected in vitro, and then grafted back into host limbs. This procedure caused duplications of anterior skeletal elements, including proximal humerus, distal radius, and digits 2 and 3. Eighty-nine percent of host wings receiving infected grafts at their anterior borders had duplications of one or more of these elements. The frequency of duplication declined dramatically when infected cells were grafted to progressively more posterior sites of host limb buds, and grafting to the posterior border had no effect at all. Several techniques were used to determine the role of infected tissue in forming skeletal duplications. First, staining with an fibroblast growth factor-2 specific monoclonal antibody showed higher than endogenous levels of fibroblast growth factor-2 expression associated with extra elements. Second, the host/donor composition of duplicated elements was determined by simultaneously infecting donor cells with viruses encoding fibroblast growth factor-2 or beta-galactosidase; donor tissue was then visualized by X-gal staining. Patterns of ectopic fibroblast growth factor-2 expression and X-gal staining confirmed the presence of infected donor tissue near duplicated structures, but the duplicated skeletal elements themselves showed very little staining. Similar results were obtained in duplications caused by infected quail wing bud cells grafted to the chick wing bud. These observations suggest that fibroblast growth factor-2-expressing donor tissue induced host tissue to form normally patterned extra elements. In support of this conclusion, implanting beads containing fibroblast growth factor-2 caused partial duplications of digit 2. These data provide the first direct evidence that fibroblast growth factor-2 plays a role in patterning in the limb bud.

scholarly journals Fibroblast Growth Factor Receptor-1 (FGFR-1) Is Essential for Normal Neural Tube and Limb Development

1997 ◽  
Vol 185 (1) ◽  
pp. 42-54 ◽  
Author(s):  
Chuxia Deng ◽  
Mark Bedford ◽  
Cuiling Li ◽  
Xiaoling Xu ◽  
Xiao Yang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Neural Tube ◽  
Limb Development ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth

Fibroblast growth factor receptors (FGFRs) and their roles in limb development

1999 ◽  
Vol 296 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Xiaoling Xu ◽  
Michael Weinstein ◽  
Cuiling Li ◽  
C.-X. Deng
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Limb Development ◽  
Growth Factor Receptors ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor Receptors

scholarly journals Fibroblast Growth Factor 4 Directs Gap Junction Expression in the Mesenchyme of the Vertebrate Limb Bud

1997 ◽  
Vol 138 (5) ◽  
pp. 1125-1137 ◽  
Author(s):  
H. Makarenkova ◽  
D.L. Becker ◽  
C. Tickle ◽  
A.E. Warner
Keyword(s):  
Growth Factor ◽  
Gap Junctions ◽  
Gap Junction ◽  
Fibroblast Growth Factor ◽  
Connexin 43 ◽  
Limb Bud ◽  
Functional Coupling ◽  
Fibroblast Growth ◽  
Mesenchyme Cells

Pattern in the developing limb depends on signaling by polarizing region mesenchyme cells, which are located at the posterior margin of the bud tip. Here we address the underlying cellular mechanisms. We show in the intact bud that connexin 43 (Cx43) and Cx32 gap junctions are at higher density between distal posterior mesenchyme cells at the tip of the bud than between either distal anterior or proximal mesenchyme cells. These gradients disappear when the apical ectodermal ridge (AER) is removed. Fibroblast growth factor 4 (FGF4) produced by posterior AER cells controls signaling by polarizing cells. We find that FGF4 doubles gap junction density and substantially improves functional coupling between cultured posterior mesenchyme cells. FGF4 has no effect on cultured anterior mesenchyme, suggesting that any effects of FGF4 on responding anterior mesenchyme cells are not mediated by a change in gap junction density or functional communication through gap junctions. In condensing mesenchyme cells, connexin expression is not affected by FGF4. We show that posterior mesenchyme cells maintained in FGF4 under conditions that increase functional coupling maintain polarizing activity at in vivo levels. Without FGF4, polarizing activity is reduced and the signaling mechanism changes. We conclude that FGF4 regulation of cell–cell communication and polarizing signaling are intimately connected.

scholarly journals Fibroblast growth factor-induced gene expression and cartilage pattern formation in chick limb bud recombinants

2001 ◽  
Vol 43 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Eiji Akiba ◽  
Sayuri Yonei-Tamura ◽  
Hiroshi Yajima ◽  
Minoru Omi ◽  
Mikiko Tanaka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Pattern Formation ◽  
Fibroblast Growth Factor ◽  
Limb Bud ◽  
Fibroblast Growth ◽  
And Cartilage

scholarly journals Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction

Development ◽  
1998 ◽  
Vol 125 (4) ◽  
pp. 753-765 ◽  
Author(s):  
X. Xu ◽  
M. Weinstein ◽  
C. Li ◽  
M. Naski ◽  
R.I. Cohen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptor ◽  
Limb Bud ◽  
Fibroblast Growth ◽  
Reciprocal Regulation ◽  
Fusion Junction ◽  
High Affinity Receptor ◽  
Membrane Spanning ◽  
Domain Iii

FGFR2 is a membrane-spanning tyrosine kinase that serves as a high affinity receptor for several members of the fibroblast growth factor (FGF) family. To explore functions of FGF/FGFR2 signals in development, we have mutated FGFR2 by deleting the entire immunoglobin-like domain III of the receptor. We showed that murine FGFR2 is essential for chorioallantoic fusion and placenta trophoblast cell proliferation. Fgfr2(DeltaIgIII/DeltaIgIII) embryos displayed two distinct defects that resulted in failures in formation of a functional placenta. About one third of the mutants failed to form the chorioallantoic fusion junction and the remaining mutants did not have the labyrinthine portion of the placenta. Consequently, all mutants died at 10–11 days of gestation. Interestingly, Fgfr2(DeltaIgIII/DeltaIgIII) embryos do not form limb buds. Consistent with this defect, the expression of Fgf8, an apical ectodermal factor, is absent in the mutant presumptive limb ectoderm, and the expression of Fgf10, a mesenchymally expressed limb bud initiator, is down regulated in the underlying mesoderm. These findings provide direct genetic evidence that FGF/FGFR2 signals are absolutely required for vertebrate limb induction and that an FGFR2 signal is essential for the reciprocal regulation loop between FGF8 and FGF10 during limb induction.

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