Rab5-mediated endocytosis of activin is not required for gene activation or long-range signalling in Xenopus.
ABSTRACT Morphogen gradients provide positional cues for cell fate specification and tissue patterning during embryonic development. One important aspect of morphogen function, the mechanism by which long-range signalling occurs, is still poorly understood. In Xenopus, members of the TGF-beta family such as the nodal-related proteins and activin act as morphogens to induce mesoderm and endoderm. In an effort to understand the mechanisms and dynamics of morphogen gradient formation, we have used fluorescently labelled activin to study ligand distribution and Smad2/Smad4 bimolecular fluorescence complementation (BiFC) to analyse, in a quantitative manner, the cellular response to induction. Our results indicate that labelled activin travels exclusively through the extracellular space and that its range is influenced by numbers of type II activin receptors on responding cells. Inhibition of endocytosis, by means of a dominant-negative form of Rab5, blocks internalisation of labelled activin, but does not affect the ability of cells to respond to activin and does not significantly influence signalling range. Together, our data indicate that long-range signalling in the early Xenopus embryo, in contrast to some other developmental systems, occurs through extracellular movement of ligand. Signalling range is not regulated by endocytosis, but is influenced by numbers of cognate receptors on the surfaces of responding cells.
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- "This internalization results in clearance of ligand from the extracellular space and is thought to be a major regulator of signal stability. For example, overexpression of a receptor of the TGFβ ligand Activin increases the frequency of Activin internalization (Hagemann et al. 2009). The accompanying decrease in signaling range may be caused by the decreased stability of Activin or the sequestration of Activin by its receptor. "
ABSTRACT: Extracellular signaling molecules have crucial roles in development and homeostasis, and their incorrect deployment can lead to developmental defects and disease states. Signaling molecules are released from sending cells, travel to target cells, and act over length scales of several orders of magnitude, from morphogen-mediated patterning of small developmental fields to hormonal signaling throughout the organism. We discuss how signals are modified and assembled for transport, which routes they take to reach their targets, and how their range is affected by mobility and stability.Developmental Cell 07/2011; 21(1):145-58. DOI:10.1016/j.devcel.2011.06.001 · 10.37 Impact Factor
Conference Paper: Using autoregressive spectral analysis to investigate weaning index[Show abstract] [Hide abstract]
ABSTRACT: Mechanical ventilation is widely used in lifesaving. But it is associated with numerous complications. Patients having weaning failure are about 7% to 19% and are subject to high mortality. To investigate this problem, we use a digital signal process approach. We record breathing data before and after weaning. The patients' weaning success and weaning failure are also recorded. The autoregressive power spectral density method is used to quantify the breathing data and investigate its rhythm changes. From spectral analysis, the power ratio of the first two peaks in the low frequency regions is calculated. We observed that patients with weaning failure have this ratio less than 1. This ratio may be a good weaning index.Engineering in Medicine and Biology, 2002. 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society EMBS/BMES Conference, 2002. Proceedings of the Second Joint; 02/2002
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ABSTRACT: Coordinated apical constriction (AC) in epithelial sheets drives tissue invagination [1, 2] and is required for diverse morphogenetic movements such as gastrulation , neurulation [4, 5], and organogenesis . We showed previously that actomyosin contractility drives AC in Xenopus laevis bottle cells ; however, it remained unclear whether it does so in concert with other processes. Here we report that endocytosis-driven membrane remodeling is required for efficient AC. We found endosomes exclusively in bottle cells in the early gastrula. Disrupting endocytosis with dominant-negative dynamin or rab5 perturbed AC, with a significant decrease in constriction rate late in the process, suggesting that endocytosis operates downstream of actomyosin contractility to remove excess membrane. Additionally, disrupting endocytosis during neurulation inhibits AC in hingepoint cells, resulting in neural tube closure defects. Thus, membrane remodeling during AC could be a general mechanism to achieve efficient invagination in embryos.Current biology: CB 02/2010; 20(3):253-8. DOI:10.1016/j.cub.2009.12.021 · 9.92 Impact Factor