13Mechanisms regulating BMP and Wnt signaling pathways have been widely studied in many 14 organisms. One of the mechanisms by which these pathways are regulated is by binding of 15 extracellular ligands. In the present study, we report studies with two BMP antagonists, gremlin 16 and noggin from Hydra vulgaris Ind-Pune and demonstrate antagonistic relationship between 17 BMP and Wnt pathways. Gremlin was ubiquitously expressed from the body column to head 18 region except in the basal disc and hypostome. During budding, gremlin was expressed 19 predominantly in the budding region suggesting a possible role in budding; this was confirmed in 20 polyps with different stages of buds. Noggin, on the other hand, was predominantly expressed in 21 the endoderm of hypostome, base of the tentacles, lower body column and at the basal disc in 22 whole polyps. During budding, noggin was expressed at the sites of emergence of tentacles 23 suggesting a role in tentacle formation. This was confirmed in alsterpaullone-treated polyps, 24 which showed noggin expression as distinct spots where ectopic organizers and ectopic tentacles 25 eventually formed. Using RT-PCR, we found that up-regulation of Wnt is accompanied with 26 down-regulation of BMP5-8b demonstrating antagonism between the two pathways. Down-27 regulation of noggin and gremlin, however, occurred only after 24 h recovery. The data suggest 28 that inhibition of BMP pathway by Wnt signaling in hydra does not directly involve noggin and 29 gremlin. Our findings indicate that the BMP/Noggin antagonism evolved early for setting up 30 2 and/or maintaining the head organizer while involvement of these BMP antagonists during 31 vertebrate axial patterning are recent evolutionary acquisitions. 32 33 Summary statement 36 We show that setting up of the Organizer by BMP/Noggin antagonism and role of BMP 37 inhibitors in tissue patterning are evolutionarily ancient, probably arising for the first time in 38 hydra 39 40 Introduction 41 Bone morphogenetic protein family, a subfamily of transforming growth factor-β (TGF-β) 42 superfamily was originally identified for role of some of its members in formation and 43 regeneration of bone in vivo. Subsequently, their roles in crucial developmental processes, such 44 as, proliferation, migration, differentiation and fate specification of embryonic cells, 45 morphogenesis and dorso-ventral patterning were discovered (Massagué, 1998; Komiya and 46 Habas, 2008). Non-optimal BMP signaling leads to a variety of developmental abnormalities and 47 disease conditions including cardiovascular diseases, symphalangism, diabetic nephropathy and 48 several types of cancers (Kattamuri et al., 2017). BMPs initiate downstream signaling by two 49 mechanisms. The first is a canonical smad-dependent pathway which involves phosphorylation 50 of Serine/Threonine kinase receptors, Type I and Type II receptor complexes (BMPRI and 51 BMPRII), and activation of smad-1/5/8. The second is a smad-independent pathway, which 52 involves TGF-β Activated Tyrosine Ki...