During development and evolution, the morphology of ectodermal organs can be modulated so that an organism can adapt to different environments. We have proposed that morphoregulation can be achieved by simply tilting the balance of molecular activity. We test the principles by analyzing the effects of partial downregulation of Bmp signaling in oral and dental epithelia of the keratin 14-Noggin transgenic mouse. We observed a wide spectrum of tooth phenotypes. The dental formula changed from 1.0.0.3/1.0.0.3 to 1.0.0.2(1)/1.0.0.0. All mandibular and M3 maxillary molars were selectively lost because of the developmental block at the early bud stage. First and second maxillary molars were reduced in size, exhibited altered crown patterns, and failed to form multiple roots. In these mice, incisors were not transformed into molars. Histogenesis and differentiation of ameloblasts and odontoblasts in molars and incisors were abnormal. Lack of enamel caused misocclusion of incisors, leading to deformation and enlargement in size. Therefore, subtle differences in the level, distribution, and timing of signaling molecules can have major morphoregulatory consequences. Modulation of Bmp signaling exemplifies morphoregulation hypothesis: simple alteration of key signaling pathways can be used to transform a prototypical conical-shaped tooth into one with complex morphology. The involvement of related pathways and the implication of morphoregulation in tooth evolution are discussed.

The feather is a complex epidermal organ with hierarchical branches and represents a multi-layered topological transformation of keratinocyte sheets. Feathers are made in feather follicles. The basics of feather morphogenesis were previously described (Lucas and Stettenheim, 1972). Here we review new molecular and cellular data. After feather buds form (Jiang et al., 2004), they invaginate into the dermis to form feather follicles. Above the dermal papilla is the proliferating epidermal collar. Distal to it is the ramogenic zone where the epidermal cylinder starts to differentiate into barb ridges or rachidial ridge. These neoptile feathers tend to be downy and radially symmetrical. They are replaced by teleoptile feathers which tend to be bilateral symmetrical and more diverse in shapes. We have recently developed a "transgenic feather" protocol that allows molecular analyses: BMPs enhance the size of the rachis, Noggin increases branching, while anti-SHH causes webbed branches. Different feather types formed during evolution (Wu et al., 2004). Pigment patterns along the body axis or intra-feather add more colorful distinctions. These patterns help facilitate the analysis of melanocyte behavior. Feather follicles have to be connected with muscles and nerve fibers, so they can be integrated into the physiology of the whole organism. Feathers, similarly to hairs, have the extraordinary ability to go through molting cycles and regenerate. Some work has been done and feather follicles might serve as a model for stem cell research. Feather phenotypes can be modulated by sex hormones and can help elucidate mechanisms of sex hormone-dependent growth control. Thus, the developmental biology of feather follicles provides a multi-dimension research paradigm that links molecular activities and cellular behaviors to functional morphology at the organismal level.