The making of a feather: Homeoproteins, retinoids and adhesion molecules

Abstract

We have been using feather development as a model for understanding the molecular basis of pattern formation and to explore the roles of homeoproteins, retinoids and adhesion molecules in this process. Two kinds of homeobox (Hox) protein gradients in the skin have been identified: a 'microgradient' within a single feather bud and a 'macrogradient' across the feather tract. The asynchronous alignment of different Hox macrogradients establishes a unique repertoire of Hox expression patterns in skin appendages within the integument, designated here as the 'Hox codes of skin appendages'. It is hypothesized that these Hox codes contribute to the phenotypic determination of skin appendages. High doses of retinoic acid cause a morphological transformation between feather and scale, while low doses of retinoic acid cause an alteration of the axial orientation of skin appendages. We have tested the ability of molecules directly involved in the feather formation process to mediate the action of the Hox codes, and surmise that adhesion molecules are potential candidates. Using specific Fabs to suppress the activity of adhesion molecules, we have found that L-CAM is involved in the formation of the hexagonal pattern, N-CAM is involved in mediating dermal condensations, tenascin is involved in feather bud growth and elongation, and integrin beta-1 is essential for epithelial-mesenchymal interactions. More work is in progress to fully understand the molecular pathways regulating the feather formation process.

cAMP, an Activator of Protein Kinase A, Suppresses the Expression of Sonic Hedgehog

“…In the db-cAMP-treated skin, the expression of Shh was suppressed ( Figure 2C, 2D). The suppression was more pronounced at the posterior of the dorsal skin than the anterior since the posterior is at a younger embryonic age (17).…”

“…In our laboratory, we have been interested in studying molecules involved in feather morphogenesis (17,18). We have previously observed that addition of forskolin, an activator of adenylyl cyclase, or dibutyryl cAMP (db-cAMP), an activator of PKA, to stage 34 (E8) skin culture media, results in the stimulation of mesenchymal condensation of feather buds (19).…”

Cellular and developmental aspects of androgenetic alopecia

“…From early on in hair follicle development, the mesenchymal precursors of the dermal papilla express cell surface adhesion molecules and produce ''sticky'' extracellular matrix molecules of various types (reviews (23,27)). This increased local cell adhesion is thought to be crucial for the initiation of mesenchymal condensations in all developing skin appendages (58,59), although cell migration factors may also be involved (60). The importance of maintaining mesenchymal cell cohesion during hair follicle development was demonstrated by Jacobson (61) who X-irradiated mouse embryos.…”

“…For example Hox genes (whose equivalents were originally found in Drosophila) are thought to be crucial for establishing the organization of many vertebrate body parts. In skin appendages Hox genes have already been shown to be associated with early patterning events (59,87). Hamilton (88) recognized a link between androgenetic alopecia and developmental processes when he noticed that the regions of hair loss in neonate infants (of both sexes) are the same as those seen in adult alopecia.…”

Follicular patterns during feather morphogenesis in relation to the formation of asymmetric feathers, filoplumes and bristles

“…The results of numerous light microscopic observations are summarized synthetically in three-dimensional models that explain in simple and visual representation the morphogenesis of these four types of pennaceous feathers. These anatomical details should help future molecular studies explaining the origin of the complex shape of feathers (Chuong 1993;Chuong & Widelitz 1999;Harris Figure 1. A, schematic drawing of a regenerating symmetric feather.…”