Abstract
In amphibians, the inhibition of bone morphogenetic protein (BMP) in the dorsal ectoderm has been proposed to be responsible for the first step of neural specification, called neural induction. We previously demonstrated that in Xenopus laevis embryos, the BMP signalling antagonist, noggin, triggers an influx of Ca2+ through voltage-dependent L-type Ca2+ channels (LTCCs), mainly via CaV1.2, and we showed that this influx constitutes a necessary and sufficient signal for triggering the expression of neural genes. However, the mechanism linking the inhibition of BMP signalling with the activation of LTCCs remained unknown. Here, we demonstrate that the transient receptor potential canonical subfamily member 1, (Trpc1), is an intermediate between BMP receptor type II (BMPRII) and the CaV1.2 channel. We show that noggin induces a physical interaction between BMPRII and Trpc1 channels. This interaction leads to the activation of Trpc1 channels and to an influx of cations, which depolarizes the plasma membrane up to a threshold sufficient to activate Cav1.2. Together, our results demonstrate for the first time that during neural induction, Ca2+ entry through the CaV1.2 channel results from the noggin-induced interaction between Trpc1 and BMPRII.
Highlights
In vertebrates, neural induction occurs during gastrulation and represents the initial event in the formation of the nervous system
Our studies demonstrate that the inhibition of bone morphogenetic protein (BMP) signalling by noggin triggers a channel activation cascade, and that the modification of the dynamic interaction between BMP receptor type II (BMPRII) and Trpc[1] is a central component of this mechanism
Dynamics during neural induction in X. laevis embryos revealed the generation of spontaneous Ca2+ transients in the most anterior part of the dorsal ectoderm, and these were shown to be associated with the expression of functional L-type Ca2+ channels (LTCCs) in the plasma membrane[7]
Summary
Neural induction occurs during gastrulation and represents the initial event in the formation of the nervous system. We describe a possible mechanism by which BMP antagonism, either in the whole X. laevis embryo or in isolated ectoderm can activate LTCCs, and we show that in the ectoderm, CaV1.2 is the main component of LTCCs. Our studies demonstrate that the inhibition of BMP signalling by noggin triggers a channel activation cascade, and that the modification of the dynamic interaction between BMPRII and Trpc[1] is a central component of this mechanism. Our studies demonstrate that the inhibition of BMP signalling by noggin triggers a channel activation cascade, and that the modification of the dynamic interaction between BMPRII and Trpc[1] is a central component of this mechanism We propose that this interaction promotes an initial influx of cations through Trpc[1], which depolarizes the membrane of ectoderm cells up to the threshold of CaV1.2 channel activation. Our new results suggest that Trpc[1] might be the missing link in the pathway between BMPRII inhibition and CaV1.2 channel activation
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