Mörsdorf D , Knabl P , Genikhovich G .

P32705-B Austrian Science Fund

	Fig. 1 BMP signalling. A Illustration of the core BMP signalling components. BMP dimers are bound and inhibited by Chordin, which blocks them from interacting with the BMP receptor complex (left). In the absence of Chordin, or after Tolloid-catalysed cleavage of Chordin and release of the BMP ligand, BMPs activate the receptor complex leading to phosphorylation of Smad1/5 (indicated by pink colour). Phosphorylated Smad1/5, together with the Co-Smad Smad4, enters the nucleus and regulates transcription of BMP target genes (right). B BMP-mediated patterning according to the shuttling model: close to the Chordin source, a high concentration of Chordin blocks BMPs from binding their receptors. The BMP-Chordin complex is diffusible and can effectively transport BMPs. Only at a distance of the Chordin source, release of BMPs from the inhibitory complex after Tolloid cleavage enables BMPs to bind receptors rather than another, yet uncleaved, Chordin molecule. In the shuttling model, BMP signalling is activated at a distance from the Chordin source, independent of the BMP source location. BMP protein concentration profile deliberately not shown since in the shuttling model it is irrelevant for the location of the BMP signalling domain (see Genikhovich et al. 2015). C BMP signalling in the source-sink model: BMP and Chordin source oppose each other. BMPs form a concentration gradient from their source and activate receptor complexes where they can bind them. Chordin forms an opposing gradient and BMP signalling is inhibited where Chordin concentration is high. Chordin acts locally to inhibit BMP signalling and does neither to inhibit, nor promote BMP signalling at a distance. Pink colour indicates phosphorylated Smad1/5 (active BMP signalling) in all panels
	Fig. 2 Involvement of BMP signalling in second body axis patterning in various phyla. Numbers at tips of the branches correspond to numbers of the sections in the text
	Fig. 3 Cnidarian BMP signalling components and cnidarian bilaterality. A Cnidarian phylogeny and distribution of the key BMP-related traits in cnidarian classes. B Cross-section of the octocoral Alcyonium digitatum (dead man’s fingers).
	Fig. 4 In Nematostella, BMP signalling controls directive axis patterning by regulating Hox genes. A Expression domains of the BMP ligands and BMP inhibitors in Nematostella early planula. B Expression of Gbx and Hox genes activated by BMP signalling in specific staggered domains along the directive axis of the Nematostella early planula and formation of the mesenteries at the boundaries of the Gbx/Hox expression. C In the primary polyp, each mesenterial segment acquires a unique Gbx/Hox code (shown on the left side of the cross-section). However, the fate of the segment is defined by one specific Hox gene or Gbx (shown on the right side of the cross-section) in a “posterior prevalence”-like manner. Knockouts of Gbx and Hox genes lead to specific homeotic transformations, where the mesenterial boundary disappears; the segment normally specified by the mutated Gbx/Hox gene fuses with and acquires the fate of its neighbouring segment located towards the BMP2/4 side of the directive axis. Please note that paired segments are called S2, S3, and S4 here rather than S2/S8, S3/S7, and S4/S6 as in He et al. (2018). D Staggered Hox expression of the bilaterian Hox genes, which demonstrate a similar regulatory behaviour. Animal sketches on D were reproduced with permission from Technau and Genikhovich 2018
	Fig. 5 BMP signalling gradient regulates orthologous genes during neurectoderm patterning in the fly and in the frog.

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