De Robertis EM , Wessely O , Oelgeschläger M , Brizuela B , Pera E , Larraín J , Abreu J , Bachiller D .

R37 HD021502-14 NICHD NIH HHS , R37 HD21502-15 NICHD NIH HHS , R37 HD021502 NICHD NIH HHS

	Fig. 4. Chordin mRNA induces secondary axes. (Upper panel) Ventral injection at the 8-cell stage lead to the formation of a twinned embryo, which contains eyes and cement gland. (Lower panel) A sagittal histologi- cal section of this embryo shows that it contains two notochords (ntc), neuraltubes(ne)andgut(1o Gand2o G).Thus,injectionofasinglemoleculecanrecapitulatethe inductions mediated by organizer grafts.
	Fig. 6. Xolloid mRNA ventralizes mesodermal pattern. Sagittal sections of tail bud stage embryos at the trunk level. The various dorso-ventral tissues are indicated in the lower panel. (A) Control. (B) Embryo after radial injection of xolloid mRNA at the four cell stage. Note the ventralization of the entire mesodermal layer in embryos expressing ectopic Xolloid metalloprotease.
	Fig. 9. CR domains present in procollagen IIA modulate BMP signaling. (A) Sequence compari- son of CR domains contained in dif- ferent extracellular matrix proteins. Coll-CR, type IIA Xenopus procollagen; CR2, murine Chordin second repeat; Nel, rat nel; Pxdasin, Drosophila peroxidasin; C. eleg. EST, C. elegans hypothetical protein containing five procollagen-like domains (accession No. CAA94866). ( Sequence alignment NOT shown) (B) Ventral injection of Xenopus procollagen IIA mRNA induces secondary axes. A construct encoding the splice variant Coll IIB lacking the CR domains is inactive in this assay (after Larraín et al., 2000). (C) Hypothetical model for the binding of BMP-4 to procollagen IIA triple helix. The cartoon shows how the presence of multiple CR domains in the procollagen triple helix could bind BMP-4 with high affinity, as is the case for Chordin. The question mark indicates the proposed protease that, like Tolloid, would release active BMPs from this extracellular reservoir of growth factors (see text) when required for tissue homeostasis.
	Fig. 10. Chordin is required for dorsal-ventral patterning in zebrafish. The Chordino mutant phenotype is due to a loss-of-function of zebrafish chordin. In mutant embryos the tail is enlarged at the ex- pense of head and anterior trunk. In situ analyses of mu- tant embryos demonstrated a reduction of the neural plate (marked by fkd3) and dorsal mesoderm (marked by shh), and an expansion of ventral mesoderm (marked by eve1) (Hammerschmidt et al., 1996). Therefore the antagonism between the Spemann-Mangold organizer secreted protein Chordin and BMP is required for the establishment of the dorsal- ventral polarity of ectoderm and mesoderm in zebrafish. Zebrafish photographs courtesy of Dr. Stefan Schulte-Merker (Tübingen).

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