Shaping organs by a wingless-int/Notch/nonmuscle myosin module which orients feather bud elongation

Abstract

How organs are shaped to specific forms is a fundamental issue in developmental biology. To address this question, we used the repetitive, periodic pattern of feather morphogenesis on chicken skin as a model. Avian feathers within a single tract extend from dome-shaped primordia to thin conical structures with a common axis of orientation. From a systems biology perspective, the process is precise and robust. Using tissue transplantation assays, we demonstrate that a "zone of polarizing activity," localized in the posterior feather bud, is necessary and sufficient to mediate the directional elongation. This region contains a spatially well-defined nuclear β-catenin zone, which is induced by wingless-int (Wnt)7a protein diffusing in from posterior bud epithelium. Misexpressing nuclear β-catenin randomizes feather polarity. This dermal nuclear β-catenin zone, surrounded by Notch1 positive dermal cells, induces Jagged1. Inhibition of Notch signaling disrupts the spatial configuration of the nuclear β-catenin zone and leads to randomized feather polarity. Mathematical modeling predicts that lateral inhibition, mediated by Notch signaling, functions to reduce Wnt7a gradient variations and fluctuations to form the sharp boundary observed for the dermal β-catenin zone. This zone is also enriched for nonmuscle myosin IIB. Suppressing nonmuscle myosin IIB disrupts directional cell rearrangements and abolishes feather bud elongation. These data suggest that a unique molecular module involving chemical-mechanical coupling converts a pliable chemical gradient to a precise domain, ready for subsequent mechanical action, thus defining the position, boundary, and duration of localized morphogenetic activity that molds the shape of growing organs.anterior-posterior axial orientation | boundary formation | denoising | morphogen gradient

Testing Turing’s theory of morphogenesis in chemical cells

“…In biology, where networks of cells arise naturally, the Turing model remains controversial because comparison of experiment and theory is hampered by incomplete knowledge of the morphogens involved in development, the rate constants of the reactions, the mechanisms of intercellular coupling, and the role of elasticity (5,7,15,16).…”

Development, Regeneration, and Evolution of Feathers

“…Meanwhile, the nuclear β-catenin signaling elevates expression of Jag1, which binds to Notch receptors on neighboring cells, generating a local positive feedback to demarcate the boundaries of the nuclear β-catenin zone. This interaction guarantees the precision of feather bud elongation orientation (33). It is interesting that Hex/Prh shows an expression pattern similar to that of Wnt-7a (34).…”

“…miRNAs function as posttranscriptional regulators by binding to the 3′ untranslated region of target mRNAs to repress translation or to cleave mRNAs. Recently, Zhang et al (51) showed that, based on the bioinformatic data, seven miRNAs collected from the follicles of growing contour and down feathers may target the genes of Wnt/β-catenin, Shh/BMP, and Notch pathways, which are important for feather morphogenesis (33, 48, 52). The differential expression profile between these two feather types was shown, suggesting the presence of a new category of molecular control, although functional data remain to be demonstrated.…”

Regulation of tissue morphodynamics: an important role for actomyosin contractility

“…A notable recent example combines kinetic and mechanics approaches to demonstrate oscillations of myosin contractile activity in the observed spatiotemporal pattern in the elongating Drosophila egg chamber [47]. Potential topics for mechanochemical modeling include a wingless-int chemical gradient specifying the precise domains of localized nonmuscle myosin II activity during chick feather morphogenesis [48] and feedback between ROCK and Shroom signaling to amplify planar polarized actomyosin contractility during Drosophila germband extension [49]. It will also be interesting to incorporate more complex feedback between intercellular forces and cellular biochemistry.…”