Positional signalling and specification of digits in chick limb morphogenesis

Tickle, Cheryll; Summerbell, Dennis; Wolpert, Lewis

doi:10.1038/254199a0

Cited by 569 publications

(215 citation statements)

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“…The precise role of gap junctions in limb development remains unclear, but previous studies suggest that morphogens may diffuse along a gradient of gap junctions and play a vital role in limb patterning and morphogenesis (Tickle et al, 1975;Allen et al, 1990;Coelho and Kosher, 1991). Retinoic acid has been linked to limb morphogenesis and patterning (Tickle et al, 1982;Summerbell, 1983;Lee and Tickle, 1985) and it has been demonstrated to reduce the number of gap junctions between cells of the AER and to alter cell morphology (Tickle et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Connexin expression and gap junction communication compartments in the developing mouse limb

Laird

Yancey

Bugga

et al. 1992

Developmental Dynamics

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Fundamental to the understanding of mouse limb morphogenesis and pattern formation is the need to elucidate the spatial and temporal distribution of gap junction proteins (connexins, Cx) and cell-cell communication compartments. To this end, we used immunofluorescence and confocal microscopy together with 3-dimensional reconstruction software to map the distribution of Cx43 and Cx32 in 11-14.5 days postcoitum (dpc) mouse limbs. Cx43 was strictly localized to the apical ectodermal ridge (AER) and nonridge ectoderm throughout all stages of mouse limb development studied. Cx32, on the other hand, was abundant in the mesenchyme with only low levels of expression in the 11-13.5 dpc ectoderm. However, at 14-14.5 dpc there was a clear increase in Cx32 expression in the ectoderm. Double labeling for connexins and confocal microscopy revealed Cx43 and Cx32 in the same optical section of the basal cells of the ectoderm but in separate plaques. Lucifer yellow dye injections showed that the cells of the AER were in direct communication with the nonridge ectoderm but dye was never observed to spread to the mesenchyme. Cells of the mesenchyme were coupled to each other but to a much lesser extent than cells of the ectoderm. Finally, although there was an increase in Cx32 expression in the ectoderm at 14-14.5 dpc, this was not correlated with any detectable change in communication compartments. Thus, the lack of dye transfer between the ectoderm and underlying mesenchyme from the peak of AER height through its decline suggests that bulk transfer of morphogens between these two layers is not necessary for mouse limb development. 0 1993 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Connexin expression and gap junction communication compartments in the developing mouse limb

Laird

Yancey

Bugga

et al. 1992

Developmental Dynamics

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“…1). In normal limb buds only tissue taken from the posterior margin of the limb had polarizing activity, and an extra digit 4 was invariably induced (see also MacCabe et al, 1973;Tickle et al, 1975;Honig and Summerbell, 1985). Tissue taken from the anterior of normal chick limb buds never specified additional digits or ectopic cartilage (4 of 4 cases; see also MacCabe et al, 1973).…”

Section: Mapping Polarizing Activity In Talpid3 Limb Budsmentioning

confidence: 99%

“…Grafts of the polarizing region to the anterior margin of the limb bud respecify anterior mesenchyme to form posterior structures such that digit duplications are induced (Saunders and Gasseling, 1968;Tickle et al, 1975). The strength of the polarizing signal, known as polarizing activity, determines the character of additional digits.…”

Section: Introductionmentioning

confidence: 99%

Expression of genes encoding bone morphogenetic proteins and sonic hedgehog in talpid (ta³) limb buds: Their relationships in the signalling cascade involved in limb patterning

Francis‐West

Robertson

Ede

et al. 1995

Developmental Dynamics

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The chicken mutant talpid3 (tu3) 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 tu3 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, tu3 anterior mesenchyme also had low polarizing activity. Application of retinoic acid or a polarizing region graft to the anterior of tu3 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 ectoderma1 ridge. In tu3 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. Fgf4 transcripts are present throughout the apical ectodermal ridge in tu3 limb buds. In the tu3 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. o 1995 Wiley-Liss, Inc.

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“…Three models have been proposed to explain the supernumerary limb formation; the polar coordinate model (22,23), the boundary model (24)(25)(26), and the polarizing zone model (27). The supernumerary limb is composed of both graft and stump cells, suggesting the occurrence of mutual and reciprocal cellular interactions between graft and stump cells during its formation (28)(29)(30)(31)(32).…”

mentioning

confidence: 99%

Expression of Sonic hedgehog gene in regenerating newt limb blastemas recapitulates that in developing limb buds

Imokawa

Yoshizato

1997

Proc. Natl. Acad. Sci. U.S.A.

119

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Positional signalling and specification of digits in chick limb morphogenesis

Cited by 569 publications

References 10 publications

Connexin expression and gap junction communication compartments in the developing mouse limb

Connexin expression and gap junction communication compartments in the developing mouse limb

Expression of genes encoding bone morphogenetic proteins and sonic hedgehog in talpid (ta³) limb buds: Their relationships in the signalling cascade involved in limb patterning

Expression of Sonic hedgehog gene in regenerating newt limb blastemas recapitulates that in developing limb buds

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Positional signalling and specification of digits in chick limb morphogenesis

Cited by 569 publications

References 10 publications

Connexin expression and gap junction communication compartments in the developing mouse limb

Connexin expression and gap junction communication compartments in the developing mouse limb

Expression of genes encoding bone morphogenetic proteins and sonic hedgehog in talpid (ta3) limb buds: Their relationships in the signalling cascade involved in limb patterning

Expression of Sonic hedgehog gene in regenerating newt limb blastemas recapitulates that in developing limb buds

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Expression of genes encoding bone morphogenetic proteins and sonic hedgehog in talpid (ta³) limb buds: Their relationships in the signalling cascade involved in limb patterning