Repression of Bmp signaling is necessary for dorsal mesodermal and neural development and is mediated through the action of Bmp antagonists, molecules secreted from dorsal tissue that can bind and prevent Bmp ligands from activating

Bone morphogenetic proteins (Bmps) and their signaling pathways are essential in the development of numerous tissues in vertebrates (reviewed in Hogan, 1996). One of the earliest developmental processes involving Bmp signaling is the establishment of the dorsoventral axis of the embryo. Overexpression experiments in the frog and fish implicate a Bmp signaling pathway in ventral cell fate specification (reviewed in Mullins, 1999; Thomsen, 1997). Mutants of bmp2b in the zebrafish (swirl mutants) demonstrate a requirement for Bmp2b in the specification of nearly all ventral cell fates (Kishimoto et al., 1997; Nguyen et al., 1998b). Repression of Bmp signaling is necessary for dorsal mesodermal and neural development and is mediated through the action of Bmp antagonists, molecules secreted from dorsal tissue that can bind and prevent Bmp ligands from activating their receptors (reviewed in Graff, 1997; Thomsen, 1997). Zebrafish mutants of chordin (chordino mutants; Fisher et al., 1997; Schulte-Merker et al., 1997), one of the Bmp antagonists, exhibit a moderate ventralized phenotype, consistent with models of chordin (chd) function. Ectopic expression and loss-of-function studies suggest that cell types derived from different dorsoventral regions of the gastrula are specified by a gradient of Bmp activity, with high levels specifying ventral and low levels lateral cell fates (Dosch et al., 1997; Jones and Smith, 1998; Knecht and Harland, 1997; Neave et al., 1997; Nguyen et al., 1998b; Wilson et al., 1997). The Bmp activity gradient is not reflected in gene expression levels of Bmp2 or Bmp4, since these genes are expressed uniformly in ventral regions or throughout the embryo (Chin et al., 1997; Nikaido et al., 1997, reviewed in Thomsen, 1997). The gradient of Bmp activity is thought to be generated by the diffusion of the Bmp antagonists, Chd, Noggin and Follistatin, from the dorsal organizer of the embryo towards ventral regions (Dosch et al., 1997; Jones and Smith, 1998; Knecht and Harland, 1997; Wilson et al., 1997). The presumptive gradients of Bmp antagonists would thus establish a gradient of Bmp 3119 Development 126, 3119-3130 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 DEV3013