Apical Ectodermal Ridge

Local application of retinoic acid to wing buds of chick embryos leads to dose- and position-dependent changes in the pattern of cellular differentiation. Early effects of retinoid treatment on the apical ectodermal ridge coordinate pattern changes and morphogenesis. The length of the apical ridge increases when additional digits will form but decreases when digits are lost. These changes in length can be understood in terms of a threshold response to the local retinoid concentration that results in either disappearance or maintenance of the ridge (Lee & Tickle, J. Embryol. exp. Morph. 90, 139–169 (1985)). Here, we have analysed the mechanisms involved in ridge disappearance by locally applying retinoic acid to the apex of stage 20 chick wing buds. With this treatment regime, low doses give duplicated digit patterns and higher doses truncations. The height of the apical ridge is progressively reduced with increasing doses of retinoid and the time course of ridge flattening indicates that the height of the ridge is correlated with bud outgrowth. With high doses of retinoic acid, the typical ridge, a pseudostratified epithelium in which the columnar cells are tightly packed, disappears and the epithelium at the tip of the bud consists of loosely packed cuboidal cells. Shortly after treatment, there is a decrease in the number of gap junctions between ridge cells. This early change in cell contacts suggests that gap junctions may be involved in maintaining epithelial morphology. When treated epithelium is recombined with untreated mesenchyme, an apical ridge is reestablished and distal structures can be generated. In contrast, when treated mesenchyme is recombined with the epithelium from normal buds, only proximal structures are formed. Therefore, retinoids can lead to a reorganization of the apical ectodermal ridge which is mediated and maintained by the mesenchyme.

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FGF-4 maintains polarizing activity of posterior limb bud cells in vivo and in vitro

Development ◽

10.1242/dev.119.1.199 ◽

1993 ◽

Vol 119 (1) ◽

pp. 199-206 ◽

Cited By ~ 21

Author(s):

A. Vogel ◽

C. Tickle

Keyword(s):

Posterior Margin ◽

Anterior Margin ◽

Marked Decrease ◽

Mesenchymal Cells ◽

Apical Ectodermal Ridge ◽

Limb Bud ◽

Posterior Limb ◽

Vertebrate Limb

The polarizing region is a major signalling tissue involved in patterning the tissues of the vertebrate limb. The polarizing region is located at the posterior margin of the limb bud and can be recognized by its ability to induce additional digits when grafted to the anterior margin of a chick limb bud. The signal from the polarizing region operates at the tip of the bud in the progress zone, a zone of undifferentiated mesenchymal cells, maintained by interactions with the apical ectodermal ridge. A number of observations have pointed to a link between the apical ectodermal ridge and signalling by the polarizing region. To test this possibility, we removed the posterior apical ectodermal ridge of chick wing buds and assayed posterior mesenchyme for polarizing activity. When the apical ectodermal ridge is removed, there is a marked decrease in polarizing activity of posterior cells. The posterior apical ectodermal ridge is known to express FGF-4 and we show that the decrease in polarizing activity of posterior cells of wing buds that normally follows ridge removal can be prevented by implanting a FGF-4-soaked bead. Furthermore, we show that both ectoderm and FGF-4 maintain polarizing activity of limb bud cells in culture.

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Limb deformity proteins: role in mesodermal induction of the apical ectodermal ridge

Development ◽

10.1242/dev.124.1.133 ◽

1997 ◽

Vol 124 (1) ◽

pp. 133-139 ◽

Cited By ~ 6

Author(s):

J. Kuhlman ◽

L. Niswander

Keyword(s):

Sonic Hedgehog ◽

Limb Development ◽

Apical Ectodermal Ridge ◽

Primary Defect ◽

Limb Deformity ◽

Normal Morphology ◽

Fibroblast Growth Factor 8 ◽

Skeletal Pattern ◽

Two Phases ◽

And Function

During early limb development, distal tip ectoderm is induced by the underlying mesenchyme to form the apical ectodermal ridge. Subsequent limb growth and patterning depend on reciprocal signaling between the mesenchyme and ridge. Mice that are homozygous for mutations at the limb deformity (ld) locus do not form a proper ridge and the anteroposterior axis of the limb is shortened. Skeletal analyses reveal shortened limbs that involve loss and fusion of distal bones and digits, defects in both anteroposterior and proximodistal patterning. Using molecular markers and mouse-chick chimeras we examined the ridge-mesenchymal interactions to determine the origin of the ld patterning defects. In the ld ridge, fibroblast growth factor 8 (Fgf8) RNA is decreased and Fgf4 RNA is not detected. In the ld mesenchyme, Sonic hedgehog (Shh), Evx1 and Wnt5a expression is decreased. In chimeras between ld ectoderm and wild-type mesenchyme, a ridge of normal morphology and function is restored, Fgf8 and Shh are expressed normally, Fgf4 is induced and a normal skeletal pattern arises. These results suggest that the ld mesenchyme is unable to induce the formation of a completely functional ridge. This primary defect causes a disruption of ridge function and subsequently leads to the patterning defects observed in ld limbs. We propose a model in which ridge induction requires at least two phases: an early competence phase, which includes induction of Fgf8 expression, and a later differentiation phase in which Fgf4 is induced and a morphological ridge is formed. Ld proteins appear to act during the differentiation phase.

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Ultrastructural analysis of the apical ectodermal ridge during vertebrate limb morphogenesis

Development ◽

10.1242/dev.41.1.223 ◽

1977 ◽

Vol 41 (1) ◽

pp. 223-232

Author(s):

John F. Fallon ◽

Robert O. Kelley

Keyword(s):

Electron Microscopy ◽

Gap Junctions ◽

Freeze Fracture ◽

Apical Ectodermal Ridge ◽

Structural Requirements ◽

Limb Morphogenesis ◽

Vertebrate Limb ◽

The Difference ◽

Freeze Fracture Electron Microscopy ◽

Fracture Electron

The fine structure of the apical ectodermal ridge of five phylogenetically divergent orders of mammals and two orders of birds was examined using transmission and freeze fracture electron microscopy. Numerous large gap junctions were found in all apical ectodermal ridges studied. This was in contrast to the dorsal and ventral limb ectoderms where gap junctions were always very small and sparsely distributed. Thus, gap junctions distinguish the inductively active apical epithelium from the adjacent dorsal and ventral ectoderms. The distribution of gap junctions in the ridge was different between birds and mammals but characteristic within the two classes. Birds, with a pseudostratified columnar apical ridge, had the heaviest concentration of gap junctions at the base of each ridge cell close to the point where contact was made with the basal lamina. Whereas mammals, with a stratified cuboidal to squamous apical ridge, had a more uniform distribution of gap junctions throughout the apical epithelium. The difference in distribution for each class may reflect structural requirements for coupling of cells in the entire ridge. We propose that all cells of the apical ridges of birds and mammals are electrotonically and/or metabolically coupled and that this may be a requirement for the integrated function of the ridge during limb morphogenesis.

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Myogenic cell movement in the developing avian limb bud in presence and absence of the apical ectodermal ridge (AER)

Development ◽

10.1242/dev.80.1.105 ◽

1984 ◽

Vol 80 (1) ◽

pp. 105-125

Author(s):

Madeleine Gumpel-Pinot ◽

D. A. Ede ◽

O. P. Flint

Keyword(s):

Cell Migration ◽

Cell Movement ◽

Host Tissue ◽

Apical Ectodermal Ridge ◽

Limb Bud ◽

Myogenic Cell ◽

Myogenic Cells ◽

Apical Direction ◽

Wing Bud ◽

Presence And Absence

Fragments of quail wing bud containing myogenic cells of somitic origin and fragments of quail sphlanchopleural tissue were introduced into the interior of the wing bud of fowl embryo hosts. No movement of graft into host tissue occurred in the control, but myogenic cells from the quail wing bud fragments underwent long migrations in an apical direction to become incorporated in the developing musculature of the host. When the apical ectodermal ridge (AER), together with some subridge mesenchyme, was removed at the time of grafting, no such cell migration occurred. The capacity of grafted myogenic cells to migrate in the presence of AER persists to H.H. stage 25, when myogenesis has begun, but premyogenic cells in the somites, which normally migrate out into the early limb bud, do not migrate when somite fragments are grafted into the wing bud. Coelomic grafts of apical and proximal wing fragments showed that apical sections of quail wing buds become invaded by myogenic cells of the host, but grafts from proximal wing bud regions do not.

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