Figure 2. The ectodomain of Tmem2 is critical for proper AVC differentiation.

In situ hybridization indicates expression of bmp4 in wild-type (A,C,E,G) embryos and Ztmem2 (B,D,F,H) mutant siblings at 48 hours post fertilization (hpf); frontal views. In wild-type (wt) embryos, concentrated expression of bmp4 is restricted to the AVC (A, arrowheads), whereas bmp4 is broadly expressed throughout the ventricle in Ztmem2 mutants (B, bracket). Expression of full-length tmem2 can restore the enriched concentration of bmp4 expression in the AVC of Ztmem2 mutants (D, arrowheads; Table 1); additionally, expression of full-length tmem2 does not affect bmp4 expression in wt siblings (C, arrowheads; Table 1). Expression of full-length tmem2 also improves cardiac looping and AVC constriction in Ztmem2 mutants (D). Similarly, expression of htrc-tmem2 can rescue the bmp4 expression pattern in Ztmem2 mutants (F, arrowheads; Table 1), but does not disrupt bmp4 expression in wt siblings (E; Table 1). Finally, as with ΔC-term and all other extracellular domain deletion variants, expression of the ΔG8 variant provides no evident rescue of the bmp4 expression pattern in Ztmem2 mutants (H, bracket; Table 1) and does not affect bmp4 expression in wt embryos (G, arrowheads; Table 1).