Hedgehog signaling in vertebrate and invertebrate limb patterning

Capdevila, Javier; Johnson, Randy L.

doi:10.1007/pl00000651

Cited by 27 publications

(21 citation statements)

References 99 publications

(81 reference statements)

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“…However, some mesodermal gene expression was lost. Shh, which depends on ridge FGF signals (reviewed by Capdevila and Johnson, 2000), was absent in T -/-limb buds (Fig. 8D).…”

Section: Potential Late Mesenchymal Effects Of Abnormal Aer Function mentioning

confidence: 95%

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A role for the mesenchymal T-box geneBrachyuryin AER formation during limb development

et al. 2003

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During limb development, several signaling centers organize limb pattern. One of these, the apical ectodermal ridge (AER), is critical for proximodistal limb outgrowth mediated by FGFs. Signals from the underlying mesoderm,including WNTs and FGFs, regulate early steps of AER induction. Ectodermal factors, particularly En1, play a critical role in regulating morphogenesis of a mature, compact AER along the distal limb apex, from a broad ventral ectodermal precursor domain. Contribution of mesodermal factors to the morphogenesis of a mature AER is less clear. We previously noted that the chick T gene (Brachyury), the prototypical T-box transcription factor, is expressed in the limb bud as well as axial mesoderm and primitive streak. Here we show that T is expressed in lateral plate mesoderm at the onset of limb bud formation and subsequently in the subridge mesoderm beneath the AER. Retroviral misexpression of T in chick results in anterior extension of the AER and subsequent limb phenotypes consistent with augmented AER extent and function. Analysis of markers for functional AER in mouse T-/- null mutant limb buds reveals disrupted AER morphogenesis. Our data also suggest that FGF and WNT signals may operate both upstream and downstream of T. Taken together, the results show that T plays a role in the regulation of AER formation,particularly maturation, and suggest that T may also be a component of the epithelialmesenchymal regulatory loop involved in maintenance of a mature functioning AER.

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“…However, some mesodermal gene expression was lost. Shh, which depends on ridge FGF signals (reviewed by Capdevila and Johnson, 2000), was absent in T -/-limb buds (Fig. 8D).…”

Section: Potential Late Mesenchymal Effects Of Abnormal Aer Function mentioning

confidence: 95%

“…Sonic hedgehog (Shh), expressed in posterior limb bud mesoderm, regulates AP polarity and number of skeletal elements. Activation of Shh also depends on ridge signals and subsequently positive feedback between FGF4 from posterior ridge and SHH maintains both signaling centers (reviewed by Capdevila and Johnson, 2000).…”

Section: Introductionmentioning

confidence: 99%

A role for the mesenchymal T-box geneBrachyuryin AER formation during limb development

et al. 2003

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“…Unlike reflecting homology between insect wing and vertebrate limbs, this indicates a general function of hh, i.e. control of cellular differentiation and proliferation (Capdevilla and Johnson 2000). Keys et al (1999) demonstrated the recruitment of a hh regulatory circuit in butterfly eyespot generation.…”

Section: The Rostrum or Labrummentioning

confidence: 98%

hedgehog is a segment polarity gene in a crustacean and a chelicerate

2004

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The evolution of arthropod segmentation has been studied by comparing expression patterns of pair-rule and segment polarity genes in various species. In Drosophila, the formation and maintenance of the parasegmental boundaries depend on the interactions between the wingless (wg), engrailed (en) and hedgehog (hh) genes. Until now, the expression pattern of hh has not been analysed to such a great extent as en or wg. We report the cloning and expression analysis of hh genes from Euscorpius flavicaudis, a chelicerate, and Artemia franciscana, a branchiopod crustacean. Our data provide evidence that hh, being expressed in the posterior part of every segment, is a segment polarity gene in both organisms. Additional hh expression sites were observed in the rostrum and appendages of Euscorpius and in the gut of Artemia. From the available data on hh expression in various bilaterians, we review the various hypotheses on the evolution of hh function and we suggest an ancestral role of hh in proctodeum specification and gut formation.

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“…Other proteins such as tout velu, disp (28), and Hip (29) have been shown to affect Shh transport but are not considered in our model. In our model Shh is assumed to diffuse freely and binds to Ptc receptors reversibly.…”

Section: Model Developmentmentioning

confidence: 99%