Retinoic acid, local cell-cell interactions, and pattern formation in vertebrate limbs

Bryant, Susan V.; Gardiner, David M.

doi:10.1016/0012-1606(92)90152-7

Cited by 147 publications

(97 citation statements)

References 121 publications

(75 reference statements)

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“…Utilizing triploidy and thymidine-labeled grafts of either cartilage or muscle, Steen (1968) showed that in axolotls, the cartilage lineage is very stable; most cartilage cells give rise to blastema cells that then redifferentiate back into cartilage. On the other hand, Steen (1968) and others have shown that connective tissue cells can give rise to cartilage (reviewed in Bryant and Gardiner, 1992). While lineage studies have not been done in newts, it seems reasonable to suggest that periosteal cells contribute to the blastema cartilage lineage.…”

Section: Discussionmentioning

confidence: 99%

Re‐programming of expression of the KGFR and bek variants of fibroblast growth factor receptor 2 during limb regeneration in newts (Notophthalmus viridescens)

Poulin

Chiu

1995

Developmental Dynamics

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We have previously shown, by in situ hybridization, that fibroblast growth factor receptor 2 (FGFRB) is present in the basal layer of wound epithelium during limb regeneration in newts (Notophthalmus viridescens). In contrast, FGFRl expression is observed throughout the blastema mesenchyme but is distinctly absent from the wound epithelium (Poulin et al. [1993] Development 1193534361). Sequence analysis revealed that we have isolated both the KGFR and bek variants of FGFR2. These two variants differ only in the second half of the last of their three (or two) Ig-like domains. In this report, we show the expression patterns of FGFRB variants during limb regeneration by in situ hybridization. During the pre-blastema stages of regeneration, FGFRB expression was observed in the basal layer of the wound epithelium and in the cells of the periosbum. The wound epithelial hybridization was observed when the KGFR-specific probe was used while the bek-specific probe hybridized to mRNA in the cells of the periosteum. As regeneration progresses to the blastema stages, KGFR expression continued to be observed in the basal layer of the wound epithelium with additional hybridization seen in the blastema mesenchyme closely associated with the bisected bones. The bek-specific hybridization pattern observed at this stage corresponds specifically to the mesenchymal hybridization. In the differentiation stages of regeneration, the mesenchymal expression of FGFR2 becomes restricted to the cells of the condensing cartilage and later to the perichondrium. Interestingly, there appears to be a dorsoventral gradient of the expression of both KGFR and bek variants of FGFR2, which are opposite each other at the later stages of regeneration. Thus, re-programming of expression of the two FGFR2 variants is required during the initial wound closure of limb regeneration. Remarkably, the expression patterns of KGFR and bek mimic those observed in the mouse limb bud during early embryonic development (Orr-Urtreger et al. [1993]

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Section: Discussionmentioning

confidence: 99%

Re‐programming of expression of the KGFR and bek variants of fibroblast growth factor receptor 2 during limb regeneration in newts (Notophthalmus viridescens)

Poulin

Chiu

1995

Developmental Dynamics

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“…Although essential for proper development, retinoids can be teratogenic if applied at inappropriate times or in abnormal concentrations. For example, retinoic acid produced duplicate limbs when applied directly to developing frog limb buds (Bryant and Gardiner, 1992), or regenerating tails (Maden, 1993), and produced deletions when applied to regenerating axolotl limbs (Scadding and Maden, 1986a). Few studies have been performed with native frogs, but Degitz et al (2000) established that retinoic acid caused hindlimb malformations in R. sylvatica that were similar to those seen in field specimens of R. septentrionalis (Gardiner and Hoppe, 1999).…”

Section: Causes Of Malformationmentioning

confidence: 99%

Prevalence of Skeletal and Eye Malformations in Frogs From North-Central United States: Estimations Based on Collections From Randomly Selected Sites

Schoff

Johnson

Schotthoefer

et al. 2003

Journal of Wildlife Diseases

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Skeletal malformation rates for several frog species were determined in a set of randomly selected wetlands in the north-central USA over three consecutive years. In 1998, 62 sites yielded 389 metamorphic frogs, nine (2.3%) of which had skeletal or eye malformations. A subset of the original sites was surveyed in the following 2 yr. In 1999, 1,085 metamorphic frogs were collected from 36 sites and 17 (1.6%) had skeletal or eye malformations, while in 2000, examination of 1,131 metamorphs yielded 16 (1.4%) with skeletal or eye malformations. Hindlimb malformations predominated in all three years, but other abnormalities, involving forelimb, eye, and pelvis were also found. Northern leopard frogs (Rana pipiens) constituted the majority of collected metamorphs as well as most of the malformed specimens. However, malformations were also noted in mink frogs (R. septentrionalis), wood frogs (R. sylvatica), and gray tree frogs (Hyla spp.). The malformed specimens were found in clustered sites in all three years but the cluster locations were not the same in any year. The malformation rates reported here are higher than the 0.3% rate determined for metamorphic frogs collected from similar sites in Minnesota in the 1960s, and thus, appear to represent an elevation of an earlier baseline malformation rate.

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“…Therefore, the hypomorphic regeneration caused by RA may be due to altered expression of the RARp gene. However, Bryant and Gardiner (1992) recently suggested that if a sufficient dose of RA is administered, most cells in the progress zone will be reprogrammed to have reduced positional diversity. Since positional differences are required to sustain growth and pattern formation, reduction of positional diversity will lead to reduced or truncated structures.…”

Section: Effects Of Ra On Regeneration Are Stage-dependentmentioning

confidence: 99%

Pattern duplication by retinoic acid treatment in the regenerating limbs of Korean salamander larvae, Hynobius leechii, correlates well with the extent of dedifferentiation

Kim

1994

Developmental Dynamics

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In the regenerating limbs of Korean salamanders, Hynobius leechii, retinoic acid (RA) induces duplication of skeletal structures in the proximodistal (PD) axis and often in the transverse axes. In the present study, the stage-dependent effects of RA for the duplication of limb skeletal structures at two amputation levels, the distal stylopodium and the distal zeugopodium, were studied using larval limbs of Korean salamanders. The results showed that the mean level of proximalization (MLP) by RA treatment increased during the stages of dedifferentiation and early bud formation while the MLP declined thereafter in both amputation levels. The decline of the MLP at the later stages of regeneration was due to the high frequency of hypomorphic regeneration or blocked regeneration. When the effects of RA treatment at two amputation levels were compared, the overall trends were similar but the actual timing was delayed for 2-4 days in the proximal level of amputation. Furthermore, the peak level of proximalization was achieved earlier and the peak level remained longer in the distal stylopodial level of amputation compared to the distal zeugopodial level of amputation. Since the histological observations revealed that the dedifferentiation period was also extended up to 2-4 days in the proximal level of amputation, the acid phosphatase activity during the course of regeneration was measured to look for a quantitative relationship between the enzyme activity and the states of dedifferentiation. The results show that the level and the duration of acid phosphatase activity in the upper arm regenerates are both higher and longer than those in the lower arm regenerates. Furthermore, RA treatment caused an increase in acid phosphatase activity. Thus our results suggest that the state of dedifferentiation might be closely linked to the extent of proximalization of regenerating limbs by RA treatment.

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Retinoic acid, local cell-cell interactions, and pattern formation in vertebrate limbs

Cited by 147 publications

References 121 publications

Re‐programming of expression of the KGFR and bek variants of fibroblast growth factor receptor 2 during limb regeneration in newts (Notophthalmus viridescens)

Re‐programming of expression of the KGFR and bek variants of fibroblast growth factor receptor 2 during limb regeneration in newts (Notophthalmus viridescens)

Prevalence of Skeletal and Eye Malformations in Frogs From North-Central United States: Estimations Based on Collections From Randomly Selected Sites

Pattern duplication by retinoic acid treatment in the regenerating limbs of Korean salamander larvae, Hynobius leechii, correlates well with the extent of dedifferentiation

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