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Zeller R Haramis AG Zuniga A McGuigan C Dono R Davidson G Chabanis S Gibson T 《Cell and tissue research》1999,298(1):85-93
Formin was originally isolated as the gene affected by the murine limb deformity (ld) mutations, which disrupt the epithelial-mesenchymal interactions regulating patterning of the vertebrate limb autopod. More
recently, a rapidly growing number of genes with similarity to formin have been isolated from many different species including fungi and plants. Genetic and biochemical analysis shows that formin family members function in cellular processes regulating either cytokinesis and/or cell polarisation. Another common feature
among formin family members is their requirement in morphogenetic processes such as budding and conjugation of yeast, establishment of
Drosophila oocyte polarity and vertebrate limb pattern formation. Vertebrate formins are predominantly nuclear proteins which control polarising activity in limb buds through establishment of the SHH/FGF-4
feedback loop. Formin acts in the limb bud mesenchyme to induce apical ectodermal ridge (AER) differentiation and FGF-4 expression in the posterior
AER compartment. Finally, disruption of the epithelial-mesenchymal interactions controlling induction of metanephric kidneys
in ld mutant embryos indicates that formin might function more generally in transduction of morphogenetic signals during embryonic pattern formation.
Received: 24 September 1998 / Accepted: 30 September 1998 相似文献
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In the development of organs, multiple morphogen sources are often involved, and interact with each other. For example, the
apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) are major morphogen sources in the limb bud formation
of vertebrates. Fgf expression in the AER and Shh expression in the ZPA are maintained by their positive feedback regulation mediated by diffusible molecules, FGF and SHH.
A recent experimental observation suggests that the FGF-signal regulates the Shh expression in a feed-forward manner with activation and repression regulatory pathways. We study the coupled dynamics of
Shh expression in the ZPA and Fgf expression in the AER, and the relationship of the relative position between AER and ZPA. We first show that with the feed-forward
regulation only, the peak of ZPA activity can be formed distant from the AER as observed experimentally. Then, we clarify
that the robustness of the ZPA spatial pattern to changes in system parameters is enhanced by adding the feedback regulation
between the AER and the ZPA. Furthermore, sensitivity analysis shows that there exists the optimal feedback strength where
the robustness is the most improved. 相似文献
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The developing forelimb is patterned along the proximal–distal and anterior–posterior axes by opposing gradients of retinoic acid and fibroblast growth factors and by graded sonic hedgehog signaling, respectively. However, how coordinated patterning along both axes is accomplished with temporal precision remains unknown. The limb molecular oscillator hairy2 was recently shown to be a direct readout of the combined signaling activities of retinoic acid, fibroblast growth factor and sonic hedgehog in the limb mesenchyme. Herein, an integrated time-space model is presented to conciliate the progress zone and two-signal models for limb patterning. We propose that the limb clock may allow temporal information to be decoded into positional information when the distance between opposing signaling gradients is no longer sufficient to provide distinct cell fate specification. 相似文献
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The egg envelope of most animal eggs is modified following fertilization, resulting in the prevention of polyspermy and hardening of the egg envelope. In frogs and mammals a prominent feature of envelope modification is N-terminal proteolysis of the envelope glycoprotein ZPA. We have purified the ZPA protease from Xenopus laevis eggs and characterized it as a zinc metalloprotease. Proteolysis of isolated egg envelopes by the isolated protease resulted in envelope hardening. The N-terminal peptide fragment of ZPA remained disulfide bond linked to the ZPA glycoprotein moiety following proteolysis. We propose a mechanism for egg envelope hardening involving ZPA proteolysis by an egg metalloprotease as a triggering event followed by induction of global conformational changes in egg envelope glycoproteins. 相似文献
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Jianxin Hu Lin He 《遗传学报》2008,35(9):517-524
Vertebrate digits are essential structures for movement,feeding and communication.Specialized regions of the developing limb bud including the zone of polarizing activity(ZPA),the apical ectodermal ridge(AER),and the non-ridge ectoderm regulate the patterning of digits.Although a series of signaling molecules have been characterized as patterning signals from the organizing centers,the delicate cellular and molecular mechanisms that interpret how these patterning signals control the detailed digit anatomy remain unclear.Recent studies from model organisms and human hand malformations provide new insights into the mechanisms regulating this process.Here,we review the current understanding of the genetic networks governing digit morphogenesis. 相似文献
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Chrisman K Kenney R Comin J Thal T Suchocki L Yueh YG Gardner DP 《Birth defects research. Part A, Clinical and molecular teratology》2004,70(4):163-171
BACKGROUND: Ethanol is known to induce a wide variety of gestational anomalies, including skeletal malformations. Gestational ethanol exposure in mice has been shown to induce postaxial digit loss (ectrodactyly). How ethanol induces limb malformations is not understood. To better understand how ethanol effects limb development, we have utilized a transgenic line of mice that expresses beta-galactosidase in the apical ectodermal ridge (AER) of the limbs throughout gestation. METHODS: Pregnant female mice were injected with 2.9, 3.4, or 3.9 gm/kg ethanol at E9.3 and E9.5; embryos were isolated at E11.25, stained for beta-galactosidase activity, and evaluated for AER defects. Based upon the pattern of defects seen, expression of FGF8 in the AER and Sonic hedgehog in the postaxial mesoderm was evaluated by in situ hybridization. RESULTS: Two distinct phenotypes were seen in response to ethanol that were dose dependent. At 2.9 gm/kg ethanol, the most prevalent phenotype was a mislocalization of the AER to regions both dorsal and ventral to the midline. A higher dosage of 3.4 gm/kg ethanol did not increase the mislocalization phenotype, but resulted in a higher frequency of postaxial loss of the AER and associated mesenchymal tissue. The highest dosage utilized (3.9 gm/kg) resulted in a high frequency of both preaxial and postaxial loss of the AER. Through in situ hybridization, we found that ethanol exposure resulted in a concomitant reduction in FGF8 expression in the AER and Sonic hedgehog expression from the zone of polarizing activity (ZPA). CONCLUSIONS: We propose a model where ethanol disrupts the AER/ZPA positive feedback loop to induce postaxial malformations. Preaxial malformations seen at higher ethanol dosage suggest FGF8 as a critical target of ethanol in producing limb defects. 相似文献
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The elaboration of the effect of retinoic acid on limb morphogenesis has prompted renewed investigation into the teratology of retinoic acid treatment, with the hope that such analysis might give insight into mechanisms of vertebrate patterning. Retinoids, their nuclear receptors and their cytoplasmic binding proteins are now known to be deployed throughout development, but the extent to which they are natural agents of morphogenesis remains obscure. The study of retinoic acid receptors may offer molecular insight into gene regulation underlying vertebrate pattern formation. 相似文献
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