Retinoid-induced alterations of segmental organization and gene expression in the mouse hindbrain

Abstract

Abstract The organization of the vertebrate body plan during development is not well understood. In invertebrates, such as Drosophila, the embryo is divided into repeated units along the anteroposterior (AP) axis; which subsequently develop into distinctive parts of the adult (for review sec Akam 1987). The process of segmentation, in which initially similar units diversify according to position, simplifies the task of constructing a complex organism. Drosophila segmentation has been well characterized at the genetic level and more than 50 genes that establish or distinguish segments have been identified (Lewis 1978; Nusslein-Volhard and Wieschaus 1980; Perrimon et al. 1982; Jurgens et al. 1984; N usslein-Volhard et al. 1984; Wicschaus et al. 1984; Schupbach and Wieschaus 1986; Akam 1987). Many of these are DNA regulators that belong to conserved families of genes that are represented in vertebrates (for reviews sec Holland and Hogan 1988; Kessell and Gruss 1990). However, not surprisingly, vertebrate embryos arc more complex than Drosophila and are not entirely segmental in form. One part of the vertebrate embryo that is clearly segmented is the hindbrain, where repetitive morphological structures (rhombomeres) have been shown to reflect an underlying segmental organization to neurogencsis (Adelman 1925; Lumsden and Keynes 1989). In mouse embryos, individual hindbrain segments show specific patterns of gene expression. Two of these segment-specific genes show an alteration in their pattern of expression when retinoic acid (RA) levels are raised. They are: Krox-20, which contains zinc finger DNA binding motifs and is expressed in rhombomercs 3 and 5 (Wilkinson et al. 1989a), and Hox-2. 9, which is expressed in the intervening rhombomere, rhombomere 4, and contains a homeobox similar to those found in Drosophila homeotic genes which confer segment identity (Murphy et al. 1989; Wilkinson et al. 1989b). Among Drosophila genes, Hox-2 .9 is most closely related to labial, which identifies an ancestral segment in the Drosophila head (Frohman et al. 1990; Murphy and Hill 1991).