Wnt signaling: why is everything so negative?

The Wnt proteins constitute a family of secreted glycoproteins the members of which have essential signaling roles during embryogenesis. The recent identification of several new regulators of this signal transduction pathway have revealed unexpectedly intricate levels of constraint on Wnt-dependent gene activation, and studies in developing embryos and in cell culture systems have allowed a more complete understanding of the functional and biochemical interactions between components of this evolutionarily conserved pathway.