FIG. 3.
Analysis of the expression of ADAM19 and neuregulin during heart and brain development by in situ mRNA hybridization and comparison of endocardial cushion development in wild-type and adam19−/− embryos. Hearts of wild-type E10.5 (a through d) and E 12.5 embryos (e through h), were probed with antisense RNA probes for mouse ADAM19 (a, b, e, and f) or neuregulin (c, d, g, and h) (51). In panels b, d, f, and h, an asterisk marks the atrioventricular endocardial cushion. In panels b and d, a thick arrow points to the atrial endocardium, where ADAM19, but little neuregulin, is expressed. A thin arrow points to the ventricular endocardium, where there is some neuregulin expression, but little ADAM19 expression. The arrowhead (b and d) points towards a limited dorsal area of the conotruncal outflow tract where expression of ADAM19 and neuregulin appear to overlap. Panels a, c, e, and g are bright field; panels b, d, f, and h are dark field. (i through n) Sections of wild-type (i and m), adam19+/− (k), or adam19−/− (j, l, and n) hearts at E10.5 (i and j), E11.5 (k and l), and E12.5 (m and n). Sections in panels k and l are of an E11.5 conotruncal endocardial cushion of a heterozygous (k) heart or homozygous ADAM19 mutant heart (l) stained with X-Gal in order to detect cells expressing lacZ under the ADAM19 promoter. Cells located below the gap indicated by an arrow in panels k and l are part of the conotruncal endocardial cushion. In panels m and n, the endocardial cushion is marked by an arrow. (o through r) Adjacent sections of the neuroepithelium of the fourth ventricle of E12.5 embryos (o and p) or of the developing spinal cord of E10.5 embryos (q and r) were probed with antisense RNA probes for mouse ADAM19 (o and q) or neuregulin (p and r) (51). In panels o and p, an arrow points to a region of enhanced coexpression of ADAM19 and neuregulin in a defined area of the neuroepithelium of the fourth ventricle. In panels q and r, thick arrows mark the dorsal root ganglion and thin arrows mark the ventral horn of the spinal cord. Abbreviations: A, atrium; V, ventricle; CT, conotruncal endocardial cushion; EC, atrioventricular endocardial cushion.