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Expression of genes encoding bone morphogenetic proteins and sonic hedgehog in talpid ( ta 3 ) limb buds: Their relationships in the signalling cascade involved in limb patterning
Author(s) -
FrancisWest P. H.,
Robertson K. E.,
Ede D. A.,
Rodriguez C.,
IzpisúaBelmonte J. C.,
Houston B.,
Burt D. W.,
Gribbin C.,
Brickell P. M.,
Tickle C.
Publication year - 1995
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/aja.1002030207
Subject(s) - zone of polarizing activity , apical ectodermal ridge , mesenchyme , limb bud , limb development , biology , sonic hedgehog , retinoic acid , anatomy , bone morphogenetic protein , mesoderm , microbiology and biotechnology , gene , genetics , embryonic stem cell , embryo
The chicken mutant talpid 3 ( ta 3 ) has polydactylous limbs with up to 7–8 morphologically similar digits. This lack of antero–posterior polarity in digit pattern is correlated with symmetrical expression of genes of the HoxD complex. We determined the distribution of polarizing activity in limb buds of the chick mutant ta 3 by assessing the ability of mesenchyme from various positions along the antero‐posterior axis to induce digit duplications when grafted anteriorly into a normal limb. Cells with highest polarizing activity were found at the posterior margin of the wing as in the polarizing region of normal limb buds. However, in contrast to normal limb buds, ta 3 anterior mesenchyme also had low polarizing activity. Application of retinoic acid or a polarizing region graft to the anterior of ta 3 limb buds changed digit morphology but did not induce digit duplications or digits with any characteristic a–p pattern. To determine which genes are associated with polarizing activity and which are associated with patterning of the digits, we examined expression of the genes Sonic hedgehog ( shh ), Bmp ‐2, and Bmp ‐7, whose expression is normally confined to the posterior margin of the early wing bud and is associated with the polarizing region. In addition, we determined the distribution of Fgf ‐ 4 transcripts which in normal limb buds are restricted to the posterior part of the apical ectodermal ridge. In ta 3 limb buds, shh expression is restricted to the posterior limb mesenchyme, which has high polarizing activity, but is not expressed in regions which have low polarizing activity. In contrast, Bmp ‐2 and Bmp ‐ 7 are expressed uniformly along the a–p axis. Fgf ‐ 4 transcripts are present throughout the apical ectodermal ridge in ta 3 limb buds. In the ta 3 mutant, there is both an abnormal distribution of signalling activity and response to polarizing signals. In addition, the dissociation between the expression of shh and Bmps suggests distinct roles for the encoded molecules in signalling and response in a–p patterning of limb buds. ©1995 Wiley‐Liss, Inc.