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Calcium transients and calcium signalling during early neurogenesis in the amphibian embryo Xenopus laevis.

Leclerc C, Néant I, Webb SE, Miller AL, Moreau M

Centre de Biologie du Développement, UMR 5547 et GDR 2688, Université Paul Sabatier, 118 route de Narbonne 31062 Toulouse, France.

Development of the vertebrate embryonic nervous system is characterized by a cascade of signalling events. In Xenopus, the initial step in this cascade results from signals emanating from the dorsal mesoderm that divert the fate of the ectoderm from an epidermal to a neural lineage. These signals include extracellular antagonists of the bone morphogenetic protein (BMP). Experiments performed with isolated ectoderm suggest that epidermis is induced by BMP, whereas neural fates arise by default following BMP inhibition; however, we show that this mechanism is not sufficient for neural determination. Ca(2+) imaging of intact Xenopus embryos reveals patterns of Ca(2+) transients in the dorsal ectoderm but not in the ventral ectoderm. These increases in intracellular calcium concentration ([Ca(2+)](i)), which occur via the activation of dihydropyridine (DHP)-sensitive Ca(2+) channels, are necessary and sufficient to orientate the ectodermal cells toward a neural fate. On the one hand, the treatments that antagonize the increase in [Ca(2+)](i), inhibit neuralization, while on the other hand, an artificial increase in [Ca(2+)](i), whatever its origin, neuralizes the ectoderm. Using these properties, we have constructed a subtractive cDNA library between untreated ectoderm and caffeine-treated ectoderm. The caffeine stimulates an increase in [Ca(2+)](i) and thus orientates the cells towards the neural pathway. We have identified early Ca(2+) target genes expressed in neural territories. One of these genes, an arginine methyl transferase, controls the expression of the early proneural gene, Zic3. Here, we discuss an alternative model where Ca(2+) plays a central regulatory role in early neurogenesis. This model integrates the activation of a Ca(2+)-dependent signalling pathway due to an influx of Ca(2+) through DHP-Ca(2+) channels. While Ca(2+) is required for neural determination, epidermal determination occurs when Ca(2+)-dependent signalling pathways are inactive.

Published 27 November 2006 in Biochim Biophys Acta, 1763(11): 1184-91.
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