Fig. analyses revealed widespread expression of mouse genes, with most prominent expression in brain. All four genes can be expressed in variously spliced mRNA isoforms. The extracellular domain name of Ten-m1 fused to an alkaline phosphatase reporter bound to specific regions in many tissues which were partially overlapping with the Ten-m1 immunostaining. Far Western assays and electronmicroscopy exhibited that Ten-m1 can bind to itself. embryo is usually controlled by genes that act in a hierarchical manner (Nsslein-Volhard and Wieschhaus, 1980; Ingham 1988; St. Johnston and Nsslein-Volhard, 1992). Maternal activities induce the expression of transcription factors, encoded by gap genes, which regulate the expression of other transcription factors encoded by pair rule genes. Pair rule genes are expressed in seven stripes along the anteriorC posterior axis of embryos. R112 Mutations in R112 pair rule genes result R112 in deletions of cuticle segments which appear in a reiterative manner along the body axis of the hatched larvae. All known pair rule genes code for transcription factors, except for R112 a gene identified independently in two laboratories and designated (Baumgartner et al., 1994) and (Levine et al., 1994). and are identical genes and mutations lead to a pair rule phenotype (Baumgartner et al., 1994; Levine et al., 1994) similar to in which every other segment is usually missing (Nsslein-Volhard et al., 1995). Despite the fact that both reports showed identical sequences, Ten-m was described as a secreted tenascin-like molecule (Baumgartner et al., 1994) and Odz as a type I transmembrane receptor (Levine et al., 1994). Tenascins are XCL1 a family of extracellular matrix proteins with a modular structure composed of fibronectin type III (FNIII) repeats, EGF-like repeats, and a COOH-terminal fibrinogen-like repeat (Erickson, 1993). Biochemical studies using a cell line indicated that Ten-m is usually a large secreted proteoglycan with chondroitinase ABC-sensitive chondroitin sulfate and/or dermatan sulfate side chains. The core protein was reported to contain EGF-like and FNIII repeats, but to lack the fibrinogen-like domain name (Baumgartner et al., 1994). Odz was isolated as a novel phosphotyrosine-containing protein (Levine et al., 1994). A transmembrane region was predicted COOH-terminal of the EGF repeats, followed by the cytoplasmic domain name containing several tyrosine kinase phosphorylation consensus sites (Levine et al., 1994). More recently, Wang et al. (1998) described a mammalian orthologue of Ten-m/Odz, termed DOC4 (downstream of chop), which is induced by the stress-induced transcription factor CHOP. The open reading frame of shares 31% sequence identity and 50% sequence similarity with Ten-m/Odz. Furthermore, DOC4 contains a short stretch of hydrophobic amino acids 400 amino acids COOH-terminal of the putative start codon. This together with the cell surface localization led to the suggestion that DOC4 may constitute a type II transmembrane molecule (Wang et al., 1998). Ten-m/Odz, as well as DOC4, contains a stretch of eight consecutive EGF-like modules which are most similar to the EGF repeats of tenascins. EGF modules are structural models of proteins or parts of protein, located extracellularly. They can occur as isolated modules such as in reelin (D’Arcangelo et al., 1995) and in selectins (Whelan, 1996), or in arrays like in notch (Fleming et al., 1997) and tenascins (Spring et al., 1989). A conserved feature of the EGF domain name in Ten-m/Odz, DOC4, and Ten-a, a molecule related to Ten-m/Odz (Baumgartner and Chiquet-Ehrismann, 1993), is the substitution of a cysteine residue with an aromatic amino acid in two of the eight EGF-like modules. This leaves two cysteines with no intramodular partner. The importance of the integrity of the cysteine patterns in EGF-like modules is usually exemplified by the functional impairment of notch 3, which has been observed in patients with an autosomal dominant disorder causing stroke (Joutel et al., 1997). The molecular basis of this disease is usually predominantly the substitution of cysteines with other amino acids in the EGF modules of notch 3. The observation that this EGF-like modules of Ten-m/Odz with five cysteines are ontogenetically conserved indicates that they are able to fold into a structure which.