Shift of Localized Growth Zones Contributes to Skin Appendage Morphogenesis: Role of the Wnt/β-catenin Pathway

Department of Pathology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA.
Journal of Investigative Dermatology (Impact Factor: 7.22). 01/2003; 120(1):20-26. DOI: 10.1046/j.1523-1747.2003.12008.x

ABSTRACT Skin appendage formation represents a process of regulated new growth. Bromodeoxyuridine labeling of developing chicken skin demonstrated the presence of localized growth zones, which first promote appendage formation and then move within each appendage to produce specific shapes. Initially, cells proliferate all over the presumptive skin. During the placode stage they are organized to form periodic rings. At the short feather bud stage, the localized growth zones shifted to the posterior and then the distal bud. During the long bud stage, the localized growth zones descended through the flank region toward the feather collar (equivalent to the hair matrix). During feather branch formation, the localized growth zones were positioned periodically in the basilar layer to enhance branching of barb ridges. Wnts were expressed in a dynamic fashion during feather morphogenesis that coincided with the shifting localized growth zones positions. The expression pattern of Wnt 6 was examined and compared with other members of the Wnt pathway. Early in feather development Wnt 6 expression overlapped with the location of the localized growth zones. Its function was tested through misexpression studies. Ectopic Wnt 6 expression produced abnormal localized outgrowths from the skin appendages at either the base, the shaft, or the tip of the developing feathers. Later in feather filament morphogenesis, several Wnt markers were expressed in regions undergoing rearrangements and differentiation of barb ridge keratinocytes. These data suggest that skin appendages are built to specific shapes by adding new cells from well-positioned and controlled localized growth zones and that Wnt activity is involved in regulating such localized growth zone activity.

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Available from: Zhicao Yue, Jun 19, 2014
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    • "Feathers and scutate scales, which are both present in extant birds, are derived from this ancestral scale, and are now individualized characters in extant birds, and exhibit distinct forms of variation. Although feathers and archosaur scales are closely related in early development, a growing body of molecular studies have documented unique regulatory mechanisms in later feather development (Harris et al. 2002; Yu et al. 2002; Chodankar et al. 2003; Harris et al. 2005; Yue et al. 2005; Yue et al. 2006), suggesting many mechanisms of later feather development are novel (Prum 1999). Interestingly, mammalian hair exhibits bcatenin localized to the anatomical placode and adjacent dermal papilla precursor cells, which is important in regulating early stages of hair development. "
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    Evolution & Development 06/2015; 17(3):185-94. DOI:10.1111/ede.12123 · 2.72 Impact Factor
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    • "Stem cell markers and PCNA and MCM2 positive cells are not highly elevated in any particular region of the regenerating tail, suggesting multiple foci of regenerative growth. This contrasts with PNCA and MCM2 immunostaining of developmental and regenerative growth zone models such as skin appendage formation [88], liver development [89], neuronal regeneration in the newt [90], and the regenerative blastema [91], which all contain localized regions of proliferative growth. Skeletal muscle and cartilage differentiation occurs along the length of the regenerating tail during outgrowth; it is not limited to the most proximal regions. "
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    PLoS ONE 08/2014; 9(8):e105004. DOI:10.1371/journal.pone.0105004 · 3.23 Impact Factor
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    • "A similar set of signaling molecules and pathways are also involved in adult feather growth and regeneration (Yu et al., 2002; Yue et al., 2006, 2012). Previous studies have characterized the expression of Wnt ligands including Wnt3a, Wnt5a, Wnt6 and Wnt8c (Chodankar et al., 2003; Yue et al., 2006). Quantifying gene expression at the whole genome scale during these processes will help evaluate the contribution of each molecule at each developmental stage. "
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