Teneurin-2 is expressed in tissues that regulate limb and somite pattern formation and is induced in vitro and in situ by FGF8

Teneurin-2 is a member of a novel family of transmembrane proteins characte rized to date in fish, birds, mammals, and Drosophila (e.g., the pair-rule gene product Ten-m). We have shown that teneurin-2 is expressed by neurons in the developing avian visual system in a pattern complementary to the exp ression of teneurin-1 and that recombinant teneurin-2 induces morphologic c hanges in neuronal cells in culture (Rubin et al., 1999). Here we have used cRNA probes to two newly identified splice variants and a teneurin-2-speci fic antibody to determine whether teneurin-2 is also expressed outside the nervous system. Both reverse transcriptase-polymerase chain reaction and in situ hybridization indicate that the three splice Variants known so far ar e coexpressed at sites of pattern formation during development, Teneurin-2 mRNAs and protein are found in the developing limbs, somites, and craniofac ial mesenchyme. In addition to expression of teneurin-2 by the apical ectod ermal ridge, teneurin-2 transcripts also appear transiently at sites of ten don development. Teneurin-2 expression patterns were strikingly similar to those of fibroblast growth factor 8 (FGF8). In agreement with the overlappi ng expression pattern, FGF8-coated beads implanted into chicken limb buds i nduced the ectopic expression of teneurin-2 and soluble FGF8 induced teneur in-2 in limb explant cultures. Thus, teneurin-2 could act downstream of FG; FS during morphogenesis. (C) 2001 Wiley-Liss, Inc.