Limb Initiation and Development Is Normal in the Absence of the Mesonephros

Abstract

With rapid progress in understanding the genes that control limb development and patterning interest is becoming focused on the factors that permit the emergence of the limb bud. The current hypothesis is that FGF-8 from the mesonephros induces limb initiation. To test this, the inductive interaction between the Wolffian duct and intermediate mesoderm was blocked rostral to the limb field, preventing mesonephric differentiation while maintaining the integrity of the limb field. The experimental outcome was monitored by following expression of cSim1 and Lmx1, molecular markers for the duct and the mesonephros, respectively. Evidence is presented that the intermediate mesoderm undergoes apoptosis when the inductive interaction with the Wolffian duct is blocked. fgf-8 expression was undetectable in the mesonephric area of embryos with confirmed absence of mesonephros; nevertheless, limb buds formed and limb development was normal. The mesonephros in general, and specifically its fgf-8 expression, was shown to be unnecessary for limb initiation and development; the hypothesis linking the mesonephros and limb development is not supported. Further studies of axial influences on limb initiation should now concentrate on medial structures such as Hensen's node and paraxial mesoderm; the alternative that no axial influences are required should also be examined.

Anteroposterior patterning in the limb and digit specification: Contribution of mouse genetics

“…Ten years ago, Fgf8 was proposed to be the relay that transfers positional information from the paraxial mesoderm to the presumptive limb field (Crossley et al, 1996). This finding, however, has not been confirmed (Fernandez-Teran et al, 1997), and the signal remains to be identified.…”

Regulation of limb bud initiation and limb‐type morphology

“…The amphibian kidney (pronephros) is located adjacent to the presumptive forelimb-forming region and although npnt is ubiquitously expressed during frog development at the time forelimb outgrowth is initiated, transcripts are enriched in pronephros. The correlation with pronephros is potentially significant since extirpation experiments in the chick have implicated nephrogenic mesoderm in forelimb initiation (Geduspan and Solursh, 1992), although this model has been recently challenged by studies in chick (Fernandez-Teran et al, 1997) and mouse (Perantoni et al, 2005). In the npnt mutant, Tbx5 expression in the presumptive forelimb area is not initiated, suggesting that nephronectinintegrin signalling acts upstream of the molecular events leading to forelimb formation.…”

Induction and prepatterning of the zebrafish pectoral fin bud requires axial retinoic acid signaling

“…However, this view has been challenged by the observation that wing buds form in experiments blocking chick mesonephric differentiation, and more specifically IM-expressed FGF8 is dispensable for mouse limb induction (Fernandez-Teran et al, 1997;Boulet et al, 2004); finally, the loss of IM cells does not affect normal development of limbs in Pax2…”

“…On the other hand, when the induction of mesonephros, a component of IM, is blocked rostral to the future limb field, limb buds nevertheless form and develop normally (Fernandez-Teran et al, 1997). In addition, elimination of FGF8 from the IM does not affect limb initiation or outgrowth (Boulet et al, 2004).…”