A crucial role of caldesmon in vascular development in vivo

Department of Pathology, Erasmus Medical Center, JNI Room 230-c, Dr Molewaterplein 50, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Cardiovascular Research (Impact Factor: 5.94). 12/2008; 81(2):362-9. DOI: 10.1093/cvr/cvn294
Source: PubMed


We explored the in vivo effects of knockdown of caldesmon on vascular development in zebrafish.
We investigated the effects of caldesmon knockdown on the vascular development in a zebrafish model with special attention for the trunk and head vessels including the aortic arches. We examined the developing fishes at various time points. The vascular abnormalities observed in the caldesmon morphants were morphologically and functionally characterized in detail in fixed and living embryos. The knockdown of caldesmon caused serious defects in vasculogenesis and angiogenesis in zebrafish morphants, and the vascular integrity and blood circulation were concomitantly impaired.
The data provide the first functional assessment of the role of caldesmon in vascular development in vivo, indicating that this molecule plays a crucial role in vasculogenesis and angiogenesis in vivo. Interfering with caldesmon opens new therapeutic avenues for anti-angiogenesis in cancer and ischaemic cardiovascular disease.

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    • "All zebrafish protocols were approved by the Institute of Animal Care as before [1] [2]. In this study, we used embryos/larvae at developing time points of 1.5 to 3 days post-fertilization (dpf) and controls The knockdown fishes included caldesmon morphants (CaD-MO)[2] and a glucose transport 1 morphants (Glut1-MO)[1] "
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    ABSTRACT: There are various zebrafish models with cardiovascular defects which adequately mimic the impaired circulation and tissue perfusion of various human cardiovascular diseases. Zebrafish embryos/larvae are optically transparent, and the systemic blood circulation can be recorded by using a microscope with video imaging. We detected a series of circulatory defects in our caldesmon and glucose transport 1 knockdown zebrafish models, including arteriovenous (AV) shunting, collateral circulation, AV fusion, vessel bifurcation, reduced or depleted regional perfusion, sinus venous (SV) rupture, and more. The quick detection by simple video imaging of various pathological states of the blood circulation in the living zebrafish embryos/larvae is non-invasive and cost-effective. The method is suitable for large scale screening of altered blood circulation in various zebrafish models with impaired cardiovascular development. This is a powerful approach of live digital data communication in biomedical research and teaching.
    Preview · Article · Aug 2013
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    • "In contrast to the wealth of information regarding CaD's activity in cultured cells, relatively little is known about its in vivo role during embryonic development. In zebrafish, CaD knockdown has been shown to cause defective cardiovascular development, with abnormal heart looping, disrupted proliferation and migration of smooth muscle, and partial loss of axial and trunk vessels (Zheng et al., 2009a, 2009b). In rat brain, both induction of CaD by glucocorticoids and inhibition of CaD by microRNA impair the radial migration of neural progenitor cells (Fukumoto et al., 2009). "
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    ABSTRACT: Caldesmon (CaD) is an important actin modulator that associates with actin filaments to regulate cell morphology and motility. Although extensively studied in cultured cells, there is little functional information regarding the role of CaD in migrating cells in vivo. Here we show that nonmuscle CaD is highly expressed in both premigratory and migrating cranial neural crest cells of Xenopus embryos. Depletion of CaD with antisense morpholino oligonucleotides causes cranial neural crest cells to migrate a significantly shorter distance, prevents their segregation into distinct migratory streams, and later results in severe defects in cartilage formation. Demonstrating specificity, these effects are rescued by adding back exogenous CaD. Interestingly, CaD proteins with mutations in the Ca(2+)-calmodulin-binding sites or ErK/Cdk1 phosphorylation sites fail to rescue the knockdown phenotypes, whereas mutation of the PAK phosphorylation site is able to rescue them. Analysis of neural crest explants reveals that CaD is required for the dynamic arrangements of actin and, thus, for cell shape changes and process formation. Taken together, these results suggest that the actin-modulating activity of CaD may underlie its critical function and is regulated by distinct signaling pathways during normal neural crest migration.
    Preview · Article · Jul 2011 · Molecular biology of the cell
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    • "The role of caldesmon in the brain is not clear. There is evidence that it may have a major role in the developing brain's vasculature (Zheng et al. 2009). A possible role in neurons could be influencing synaptic plasticity by transferring signals from receptors to the actin cytoskeleton, as proposed by Represa et al. (1995) and K. Agassandian and Cassell (2008). "
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    ABSTRACT: The author has recently reported the distribution of the cytoskeleton-associated protein caldesmon in spleen and lymph nodes detected with different antibodies against caldesmon (J Histochem Cytochem 58:183-193, 2010). Here the author reports the distribution of caldesmon in the CNS and ganglia of the mouse using the same antibodies. Western blot analysis of mouse brain and spinal cord showed the preponderance of l-caldesmon and suggested at least two l-caldesmon isoforms in the brain. Immunostaining revealed the predominant reactivity of smooth muscle cells and cells resembling pericytes of many large and small blood vessels, ependymocytes, and secretory cells of the pineal gland and pituitary gland. Neuronal perikarya and neuropil in general displayed no or weak immunoreactivity, but there was stronger labeling of neuronal perikarya in dorsal root and trigeminal ganglia. In the brain, staining of the neuropil was stronger in the molecular layers of the dentate gyrus and cerebellum. Results show that caldesmon is expressed in many different cell types in the CNS and ganglia, consistent with the notion that l-caldesmon is ubiquitously expressed, but it appears most concentrated in smooth muscle cells, pericytes, epithelial cells, secretory cells, and neuronal perikarya in dorsal root and trigeminal ganglia.
    Preview · Article · Mar 2011 · Journal of Histochemistry and Cytochemistry
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