Kriebitz Nadja N, Kiecker Clemens, McCormick Laura, Lumsden Andrew, Graham Anthony, Bell Esther
MRC Centre for Developmental Neurobiology, 4th Floor New Hunts House, Kings College London, Guy's Campus, London SE1 1UL, UK.
Dev Biol. 2009 Dec 15;336(2):280-92. doi: 10.1016/j.ydbio.2009.10.013. Epub 2009 Oct 15.
The epibranchial placodes generate the neurons of the geniculate, petrosal, and nodose cranial sensory ganglia. Previously, it has been shown that bone morphogenetic proteins (BMPs) are involved in the formation of these structures. However, it has been unclear as to whether BMP signalling has an ongoing function in directing the later development of the epibranchial placodes, and how this signalling is regulated. Here, we demonstrate that BMPs maintain placodal neurogenesis and that their activity is modulated by a member of the Cerberus/Dan family of BMP antagonists, Protein Related to Dan and Cerberus (PRDC). We find that Bmp4 is expressed in the epibranchial placodes while Bmp7 and PRDC are expressed in the pharyngeal pouches. The timing and regional expression of these three genes suggest that BMP7 is involved in inducing placode neurogenesis and BMP4 in maintaining it and that BMP activity is modulated by PRDC. To investigate this hypothesis, we have performed both gain- and loss- of-function experiments with PRDC and find that it can modulate the BMP signals that induce epibranchial neurogenesis: a gain of PRDC function results in a loss of Bmp4 and hence placode neurogenesis is inhibited; conversely, a loss of PRDC function induces ectopic Bmp4 and an expansion of placode neurogenesis. This modulation is therefore necessary for the number and positioning of the epibranchial neurons.
鳃上神经节产生膝状、岩状和结节状颅感觉神经节的神经元。此前已表明，骨形态发生蛋白（BMPs）参与这些结构的形成。然而，BMP信号是否在指导鳃上神经节的后期发育中具有持续作用，以及该信号如何被调节尚不清楚。在此，我们证明BMPs维持神经节神经发生，并且它们的活性受BMP拮抗剂Cerberus/Dan家族成员——与Dan和Cerberus相关的蛋白（PRDC）调节。我们发现Bmp4在鳃上神经节中表达，而Bmp7和PRDC在咽囊中表达。这三个基因的表达时间和区域表明，BMP7参与诱导神经节神经发生，BMP4参与维持神经发生，并且BMP活性受PRDC调节。为了验证这一假设，我们对PRDC进行了功能获得和功能丧失实验，发现它可以调节诱导鳃上神经发生的BMP信号：PRDC功能获得导致Bmp4缺失，从而抑制神经节神经发生；相反，PRDC功能丧失诱导异位Bmp4表达并导致神经节神经发生扩展。因此，这种调节对于鳃上神经元的数量和定位是必要的。
