IMMUNOHISTOCHEMICAL LOCALIZATION OF TGF-BETA-1, TGF-BETA-2, AND TGF-BETA-3 IN THE MOUSE EMBRYO - EXPRESSION PATTERNS SUGGEST MULTIPLE ROLES DURING EMBRYONIC-DEVELOPMENT

Isoform-specific antibodies to TGF-beta-1, TGF-beta-2, and TGF-beta-3 proteins were generated and have been used to examine the expression of these factors in the developing mouse embryo from 12.5-18.5 d post coitum (d.p.c.). These studies demonstrate the initial characterization of both TGF-beta-2 and beta-3 in mammalian embryogenesis and are compared with TGF-beta-1. Expression of one or all three TGF-beta proteins was observed in many tissues, e.g., cartilage, bone, teeth, muscle, heart, blood vessels, lung, kidney, gut, liver, eye, ear, skin, and nervous tissue. Furthermore, all three TGF-beta proteins demonstrated discrete cell-specific patterns of expression at various stages of development and the wide variety of tissues expressing TGF-beta proteins represent all three primary embryonic germ layers. For example, specific localization of TGF-beta-1 was observed in the lens fibers of the eye (ectoderm), TGF-beta-2 in the cortex of the adrenal gland (mesoderm), and TGF-beta-3 in the cochlear epithelium of the inner ear (endoderm). Compared to the expression of TGF-beta mRNA transcripts in a given embryonic tissue, TGF-beta proteins were frequently colocalized within the same cell type as the mRNA, but in some cases were observed to localize to different cells than the mRNA, thereby indicating that a complex pattern of transcription, translation, and secretion for TGF-beta-s 1-3 exists in the mouse embryo. This also indicates that TGF-beta-1, beta-2, and beta-3 act through both paracrine and autocrine mechanisms during mammalian embryogenesis.