Local Inhibitory Action of BMPs and Their Relationships with Activators in Feather Formation: Implications for Periodic Patterning

Abstract

The formation of periodic patterns is fundamental in biology. Theoretical models describing these phenomena have been proposed for feather patterning; however, no molecular candidates have been identified. Here we show that the feather tract is initiated by a continuous stripe of Shh, Fgf-4, and Ptc expression in the epithelium, which then segregates into discrete feather primordia that are more strongly Shh and Fgf-4 positive. The primordia also become Bmp-2 and Bmp-4 positive. Bead-mediated delivery of BMPs inhibits local feather formation in contrast with the activators, SHH and FGF-4, which induce feather formation. Both FGF-4 and SHH induce local expression of Bmp-4, while BMP-4 suppresses local expression of both. FGF-4 also induces Shh. Based on these findings, we propose a model that involves (1) homogeneously distributed global activators that define the field, (2) a position-dependent activator of competence that propagates across the field, and (3) local activators and inhibitors triggered in sites of individual primordia that act in a reaction-diffusion mechanism. A computer simulation model for feather pattern formation is also presented.

Expression and regulation of groucho‐related genes in the embryonic chicken feather bud

“…Forced expression of either BMP-2 or -4 in the epidermis of the forming tract prevents both the morphologic and gene expression changes associated with the formation of an epidermal placode in the vicinity of the infection (Noramly and Morgan, 1998). Ectopic BMP expression suppressed bud formation as reported previously (Jung et al, 1998;Noramly and Morgan, 1998). In areas of elevated BMP signaling, Grg gene expression was also suppressed (Fig.…”

“…BMP-2 is both necessary and sufficient to inhibit adjacent epidermal cells from adopting the placodal fate (Jung et al, 1998;Noramly and Morgan, 1998). Thus, the interplay between signals spreading through the tract that promote activation of the ␤-catenin pathway in the epidermis and inhibitory signals (BMP-2) expressed by the nascent placode serve to specify the size and position of the feather rudiments.…”

“…Morgan, unpublished data). If so, one aspect of lateral inhibition involves limiting responsiveness to this signal (Jung et al, 1998;Noramly and Morgan, 1998;B.A. Morgan, unpublished data).…”

Variation in the ovine WFIKKN2 gene

“…It may therefore be associated with unique traits (such as wool traits) in Merino sheep. WFIKKN2 can bind bone morphogenetic protein 2 (BMP2) and bone morphogenetic protein 4 (BMP4) with relatively high affinity (Szlama et al, 2010), and the genes for these two proteins are expressed in hair shaft precursor cells (Kulessa et al, 2000), while ectopic expression of BMP2 or BMP4 suppresses the formation of feather buds in chick embryos (Jung et al, 1998;Noramly and Morgan, 1998). Additionally, because WFIKKN2 possesses a follistatin-domain, it may have an overlapping function with follistatin, which has been shown to be an important regulator of cell proliferation, differentiation and apoptosis in hair follicle initiation, hair cycling, normal skin homeostasis and wound healing (McDowall et al, 2008).…”

Intercellular growth factor signaling and the development of mouse tracheal submucosal glands

“…In the developing hair follicle, Bmp4 expression is first restricted to the mesenchymal condensation beneath future placodes. Here, it is thought to control follicle spacing by acting as an inhibitor of placode formation in the surrounding regions (Jung et al, 1998;Noramly and Morgan, 1998;Wilson et al, 1999). In contrast, we found that Bmp4 is expressed throughout the tracheal mesenchyme during the development of the SMGs so that it presumably cannot be functioning to control their spacing.…”