Proteolytic processing of the Drosophila Spatzle protein by Easter generates a dimeric NGF-like molecule with ventralising activity

Biochemical interactions underlying the generation of the ventralising signal during Drosophila embryogenesis were investigated by the expression of recombinant Easter and Spatzle proteins. An active form of Easter protease cleaves the Spatzle protein, generating a carboxyterminal polypeptide fragment which, when microinjected into the perivitelline space of a spatzle deficient embryo, directs production of ventrolateral pattern elements. This Spatzle carboxyterminal fragment is a disulfide-linked dimer and modelling suggests that the core disulfide bonds and dimer arrangement of this fragment are highly similar to vertebrate nerve growth factor. Thus Spatzle is a member of a new family of neurotrophin-like signalling molecules in invertebrate development. (C) 1998 Elsevier Science Ireland Ltd.