SUMMARY β-catenin signaling can initiate feather bud development

The feather tract provides an ideal system to dissect the interactions between cells generating pattern in a competent field. The coordinated subdivision of ectoderm and dermis into follicular and interfollicular fates, as well as subsequent patterning within individual buds, is achieved in part by opposing influences of intercellular signaling molecules expressed in the forming tract (Song et al., 1996; Crowe et al., 1998; Jung et al., 1998; Noramly and Morgan, 1998). Buds form in a number of discrete tracts (pterylae) in reproducible position and sequence within the embryo separated by featherless (apteric) regions. Tract development begins with formation of the dense dermis, a 2to 3-fold increase in cell density in the mesenchyme underlying the presumptive pterylae. This dense dermis forms throughout the tract and no morphological or molecular distinction between presumptive follicular and interfollicular fates is observable at this stage. Tissue recombination experiments have identified a primary inductive signal that originates in the dense dermis and causes the first morphological distinction between the follicle and surrounding interfollicular skin: the formation of a placode of columnar cells in the epidermis (reviewed in Sengel, 1976; Dhouailly et al., 1998). This epidermal placode in turn signals to the dermis and induces formation of the dermal condensation which acquires its own inductive properties. Reciprocal interactions between these two signaling centers cause the subsequent outgrowth and patterning of the bud. Within each tract, a single row of buds is formed first and sequential rows of buds are added subsequently as the inductive signal propagates through the tract. As a result, a tract contains buds at successive stages of development arranged in an ordered array. The formation of individual buds and their position relative to each other in a tract are intimately linked. The position of buds within a row, and the spacing between rows is mediated in part by lateral inhibition from previously formed buds (Davidson, 1983; Jung et al., 1998; Noramly and Morgan, 1998). Although the sources of inductive signals and the role of lateral inhibition have been established by tissue recombination experiments, the mechanisms by which pattern is generated remain ill defined. For example, it is unclear whether the inductive signal from the dermis that initiates placode formation is localized beneath the prospective bud, or whether a more generalized inductive signal results in a localized response in the ectoderm as a result of patterning interactions within this layer. To better understand this process, it is necessary to identify the signals that mediate these inductive interactions. Only then can we assess the relative contributions played by localized expression of inductive signals in the dermis and spatial restrictions in responsiveness in the ectoderm to specify the position of the ectodermal placodes. Several of the molecules that mediate inductive signaling during feather tract formation have been identified, including members of the Bone Morphogenetic Protein (BMP), Fibroblast Growth Factor (FGF), Hedgehog and Notch/Delta families (Song et al., 1996; Ting-Berreth and Chuong, 1996; Crowe et al., 1998; Jung et al., 1998; Morgan et al., 1998; 3509 Development 126, 3509-3521 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 DEV6407