A growth-promoting influence from the mesonephros during limb outgrowth

doi:10.1016/0012-1606(92)90230-E

Developmental Biology

Volume 151, Issue 1, May 1992, Pages 242-250

https://doi.org/10.1016/0012-1606(92)90230-E Get rights and content

Abstract

It has been suggested that the mesonephros has a role in normal limb development. This hypothesis was directly tested by removing the mesonephros adjacent to the presumptive limb region of stage 12–18 chick embryos using microsurgery or laser ablation. The experimental manipulation resulted in reduced limb outgrowth on the operated side. The poor limb outgrowth was correlated with either the lack of or the presence of a rudimentary mesonephros on the operated side. Furthermore, the presence of nephric tissue in limb bud organ culture enhanced growth and morphological differentiation of cartilage formed in culture. In vivo, the influence of the mesonephros resulted in significantly higher cell proliferation in the adjoining medial half of the limb mesoderm compared with the lateral half. The removal of the mesonephros adjoining the prospective limb region reduced the number of dividing cells in the medial mesoderm. The higher proliferation in the medial limb mesoderm is significant to limb outgrowth since grafting experiments showed that most of the cells that form the limb are derived from the medial mesoderm. The results suggest that the influence from the mesonephros may provide some signal for limb outgrowth.

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Cited by (59)

Bones and Cartilage: Developmental and Evolutionary Skeletal Biology
2015, Bones and Cartilage: Developmental and Evolutionary Skeletal Biology
The secreted integrin ligand nephronectin is necessary for forelimb formation in Xenopus tropicalis
2011, Developmental Biology
Citation Excerpt :
The mouse mutant, however, shows ablation of the metanephros (a kidney component not present in amphibians), mirroring the kidney phenotype observed in deletions of the α8 integrin subunit of the npnt receptor (Muller et al., 1997). A role for nephrogenic mesoderm in forelimb outgrowth was originally suggested by extirpation studies in chick that disrupted wing formation (Geduspan and Solursh, 1992), and gained support with the demonstration that Fgf applied to the flank could induce ectopic limb bud outgrowth (Cohn et al., 1995) and that the developing mesonephros expresses Fgf8 (Crossley and Martin, 1995). This model was recently challenged by reports that forelimb initiation is normal in the absence of the mesonephros (Fernandez-Teran et al., 1997) and that conditional deletion of Fgf8 in mouse mesonephros has no effect on forelimb bud initiation (Perantoni et al., 2005).
While limb regeneration has been extensively studied in amphibians, little is known about the initial events in limb formation in metamorphosing anurans. The small secreted integrin ligand nephronectin (npnt) is necessary for development of the metanephros in mouse. Although expressed in many tissues, its role in other developmental processes is not well-studied. Here we show that a transgene insertion that disrupts this gene ablates forelimb formation in Xenopus tropicalis. Our results suggest a novel role for integrin signalling in limb development, and represent the first insertional phenotype to be cloned in amphibians.
Drosophila Limb Development
2005, Comprehensive Molecular Insect Science
The roles of Fgf4 and Fgf8 in limb bud initiation and outgrowth
2004, Developmental Biology
Although numerous molecules required for limb bud formation have recently been identified, the molecular pathways that initiate this process and ensure that limb formation occurs at specific axial positions have yet to be fully elucidated. Based on experiments in the chick, Fgf8 expression in the intermediate mesoderm (IM) has been proposed to play a critical role in the initiation of limb bud outgrowth via restriction of Fgf10 expression to the appropriate region of the lateral plate mesoderm. Contrary to the outcome predicted by this model, ablation of Fgf8 expression in the intermediate mesoderm before limb bud initiation had no effect on initial limb bud outgrowth or on the formation of normal limbs. When their expression patterns were first elucidated, both Fgf4 and Fgf8 were proposed to mediate critical functions of the apical ectodermal ridge (AER), which is required for proper limb bud outgrowth. Although mice lacking Fgf4 in the AER have normal limbs, limb development is severely affected in Fgf8 mutants and certain skeletal elements are not produced. By creating mice lacking both Fgf4 and Fgf8 function in the forelimb AER, we show that limb bud mesenchyme fails to survive in the absence of both FGF family members. Thus, Fgf4 is responsible for the partial compensation of distal limb development in the absence of Fgf8. A prolonged period of increased apoptosis, beginning at 10 days of gestation in a proximal–dorsal region of the limb bud, leads to the elimination of enough mesenchymal cells to preclude formation of distal limb structures. Expression of Shh and Fgf10 is nearly abolished in double mutant limb buds. By using a CRE driver expressed in both forelimb and hindlimb ectoderm to inactivate Fgf4 and Fgf8, we have produced mice lacking all limbs, allowing a direct comparison of FGF requirements in the two locations.
Hypothesis: Hemimelia and the maintenance of pentadactyly?
2001, Journal of Theoretical Biology
The limbs of extant terrestrial vertebrates possess five or fewer digits, yet, polydactyly is accepted as being the ancestral state. Therefore, I propose a hypothesis to account for the maintenance of digital number at five or fewer digits, based on a selective disadvantage associated with polydactylous states in terrestrial vertebrates. This disadvantage is not associated with the polydactyly per se, but rather with the hemimelia which is a common feature of polydactylies in mammals. Hemimelia causes a twisting, or luxation, of the distal segment of the limb, which is due to a malformation of the radius/tibia of the limb. This defect results in the limb being held in an abnormal gait, which causes problems in the locomotion of the animal which would compromise their ability to flourish. Therefore, the abnormal gait and torsion of the limb caused by the hemimelia is acting as a stabilizing force to maintain the dactyly of the tetrapod limb with five or fewer digits.
WNT signals control FGF-dependent limb initiation and AER induction in the chick embryo
2001, Cell
A regulatory loop between the fibroblast growth factors FGF-8 and FGF-10 plays a key role in limb initiation and AER induction in vertebrate embryos. Here, we show that three WNT factors signaling through β-catenin act as key regulators of the FGF-8/FGF-10 loop. The Wnt-2b gene is expressed in the intermediate mesoderm and the lateral plate mesoderm in the presumptive chick forelimb region. Cells expressing Wnt-2b are able to induce Fgf-10 and generate an extra limb when implanted into the flank. In the presumptive hindlimb region, another Wnt gene, Wnt-8c, controls Fgf-10 expression, and is also capable of inducing ectopic limb formation in the flank. Finally, we also show that the induction of Fgf-8 in the limb ectoderm by FGF-10 is mediated by the induction of Wnt-3a. Thus, three WNT signals mediated by β-catenin control both limb initiation and AER induction in the vertebrate embryo.

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^☆: Supported by NIH Grant HD 05505.

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Developmental Biology

Abstract

References (24)

Studies on the ability of embryonic mesonephros explants to form cartilage

Dev. Biol

Normal embryology and teratogenesis

Am. J. Obst. Gynecol

Trans-filter propagation of apical ectodermal ridge maintenance factor in the chick embryo wing bud

Dev. Biol

The initiation of limb outgrowth in the embryonic chick

Dev. Biol

The regulative ability of the limb regeneration blastema of Nothopthalmus viridescens: Experiments in situ

Arch Entwicklungsmech. Org

On axiation and symmetry in transplanted wing of the chick

J. Exp. Zool

Morphogenetic and axial self-differentiation of transplanted limb primordia of 2-day chick embryos

J. Exp. Zool

A series of normal stages in the development of the chick embryo

J. Morphol

Cell division in the early growth and morphogenesis of the chick limb

Nature

Animal Tissue Techniques

Transfilter evidence for a zone of polarizing activity participating in limb morphogenesis

J. Embryol. Exp. Morphol

Sur les relations entre le mesoderme somitique et mesoderme somatopleural avant et au cours de l'induction primaire des membres de l'embryon du Poulet

C.R. Hebd. Seances Acad. Sci. Paris D

Cited by (59)

Bones and Cartilage: Developmental and Evolutionary Skeletal Biology

The secreted integrin ligand nephronectin is necessary for forelimb formation in Xenopus tropicalis

Drosophila Limb Development

The roles of Fgf4 and Fgf8 in limb bud initiation and outgrowth

Hypothesis: Hemimelia and the maintenance of pentadactyly?

WNT signals control FGF-dependent limb initiation and AER induction in the chick embryo

Full paperA growth-promoting influence from the mesonephros during limb outgrowth☆

Abstract

Dev. Biol

Am. J. Obst. Gynecol

Dev. Biol

Dev. Biol

The regulative ability of the limb regeneration blastema of Nothopthalmus viridescens: Experiments in situ

Arch Entwicklungsmech. Org

On axiation and symmetry in transplanted wing of the chick

J. Exp. Zool

Morphogenetic and axial self-differentiation of transplanted limb primordia of 2-day chick embryos

J. Exp. Zool

A series of normal stages in the development of the chick embryo

J. Morphol

Cell division in the early growth and morphogenesis of the chick limb

Nature

Animal Tissue Techniques

Transfilter evidence for a zone of polarizing activity participating in limb morphogenesis

J. Embryol. Exp. Morphol

Sur les relations entre le mesoderme somitique et mesoderme somatopleural avant et au cours de l'induction primaire des membres de l'embryon du Poulet

C.R. Hebd. Seances Acad. Sci. Paris D

Full paper
A growth-promoting influence from the mesonephros during limb outgrowth☆