Embryonic Patterning: To BMP or Not to BMP, That Is the Question

tissue. That is, the dorsal donor graft redirects the fate Vertebrates begin life as a seemingly unpatterned clusof the host’s ventral mesoderm into properly organized ter of cells. Rapidly, however, the shape of an embryo dorsal mesoderm with a notochord and muscle segchanges and begins to acquire an easily recognizable ments. The donor tissue also repatterns the host’s venpattern. This formation of pattern occurs largely along tral ectoderm, initially fated to become skin, into an two distinct axes, anterior–posterior and dorsal–ventral. organized neural tube, a dorsal ectodermal derivative. The molecular mechanisms that underlie this transition Therefore, in what appear to be parallel processes, the from a radially symmetric egg to a patterned embryo donor graft converts the fate of two germ layers from remain largely unknown. Classical embryological experventral to dorsal. This alteration in cell fate is often iments have provided many insights into the type of termed dorsalization in the mesoderm and neural inducactivities (signals) that may be important in pattern fortion in the ectoderm. Because of these properties, the mation. For example, explants of dorsal tissues alter small dorsal region of the amphibian embryo is called ventral tissues to dorsal fates while ventral cells have the Spemann organizer; the homolog in the chick and no effect on dorsal cells. Based on this ability of the the mouse is called the node. dorsal cells, a model of dorsal–ventral patterning of the Additional support for a dorsal-determining signal is embryonic germ layers has been generated (reviewed provided by studying ventral and dorsal explants (Figure by Slack, 1991; Harland, 1994). In this model, ventral 2C) (reviewed by Smith, 1989). When explants of ventral tissue is thought to be the ground state and dorsal tistissue are cultured in isolation, they heal and form an sues to require the presence of additional or stronger unpatterned ball of cells. Histological analysis reveals signals. Recent molecular studies contradict this dorsala loose mix of mesenchyme and blood-like cells; that dominant model. These studies indicate that an active is, only ventral tissues are present. In contrast, explants BMP signal is required to form ventral tissues and that of dorsal tissue undergo dramatic movements and aploss of this active ventral signal results in formation of pear as organized, elongated structures; mimicking dorsal tissues (reviewed by Harland,1994; Hogan, 1996). what occurs normally in the developing embryo. HistoThis paradox appears to be reconciled by the recent logical analysis of these dorsal explants demonstrates discovery that dorsal signals bind BMP4 with high affinthe presence of appropriately patterned dorsal tissues, ity and thereby block BMP signaling (Piccolo et al., 1996; such as the notochord and muscle, and the absence of Zimmerman et al., 1996). That is, the dorsal signals funcventral tissues. These observations that ventral explants tion by antagonizing the active ventral signal, BMP4, are unpatterned and that dorsal explants are organized rather than by directly promoting dorsal fates. were thought to suggest that the ventral tissue is in an In vertebrates, the three embryonic germ layers— ‘‘unactivated groundstate’’ and that the patterned dorsal ectoderm, mesoderm, and endoderm—are patterned.