Regulation of msx by BMP gradient is essential for neural crest specification

C. TRÍBULO; M. AYBAR; A. GLAVIC; C. ARAYA; J. DE CALISTO; R. MAYOR

Tallinn, Estonia, Europa

Congreso; 2004 Meeting of International Research Scholars, Howard Hughes Medical Institue; 2004

Howard Hughes Medical Institute

The neural crest originates at the border between the neural plate and the future epidermis. It gives rise to numerous and diverse cell types, including the peripheral nervous system, the cranofacial skeleton, and pigment cells. Although considerable progress has been made recently in the molecular characterization of neural crest–inducing factors, relatively little is known about the genetic cascade of transcription factors that determine the specification of the neural crest at the neural plate border. There is evidence in Xenopus and zebrafish embryos that the neural crest is specified at the border of the neural plate by a precise threshold concentration of a BMP gradient. To understand the molecular mechanism by which a gradient of BMP is able to specify the neural crest, we analyzed how the expression of the BMP target, msx, is regulated and the role that msx plays on neural crest specification. In Xenopus and zebrafish embryos, we analyzed msx expression after experimental modification of the level of BMP activity by three different methods. All the results show that a reduction in the level of BMP activity leads to an increase in the expression of msx in the neural plate border. Interestingly, we show that there is a specific concentration of BMP that induces msx1 expression. In addition, we have analyzed the role that msx1 plays in neural crest specification. We show that msx1 expression is necessary and sufficient for early neural crest specification. We propose a model whereby a gradient of BMP activity specifies the expression of msx in the neural folds, and that this expression is essential for the early specification of the neural crest.