title: In search of the Golden Fleece: unraveling principles of morphogenesis by studying the integrative biology of skin appendages.
abstract: The mythological story of the Golden Fleece symbolizes the magical regenerative power of skin appendages. Similar to the adventurous pursuit of the Golden Fleece by the multi-talented Argonauts, today we also need an integrated multi-disciplined approach to understand the cellular and molecular processes during development, regeneration and evolution of skin appendages. To this end, we have explored several aspects of skin appendage biology that contribute to the Turing activator/inhibitor model in feather pattern formation, the topo-biological arrangement of stem cells in organ shape determination, the macro-environmental regulation of stem cells in regenerative hair waves, and potential novel molecular pathways in the morphological evolution of feathers. Here we show our current integrative biology efforts to unravel the complex cellular behavior in patterning stem cells and the control of regional specificity in skin appendages. We use feather/scale tissue recombination to demonstrate the timing control of competence and inducibility. Feathers from different body regions are used to study skin regional specificity. Bioinformatic analyses of transcriptome microarrays show the potential involvement of candidate molecular pathways. We further show Hox genes exhibit some region specific expression patterns. To visualize real time events, we applied time-lapse movies, confocal microscopy and multiphoton microscopy to analyze the morphogenesis of cultured embryonic chicken skin explants. These modern imaging technologies reveal unexpectedly complex cellular flow and organization of extracellular matrix molecules in three dimensions. While these approaches are in preliminary stages, this perspective highlights the challenges we face and new integrative tools we will use. Future work will follow these leads to develop a systems biology view and understanding in the morphogenetic principles that govern the development and regeneration of ectodermal organs.
authors: Department of Pathology, School of Medicine, University of Southern California, HMR 315B, 2011 Zonal Ave., Los Angeles, CA 90033, USA.
authors: Michael W
authors: MW
authors: Hughes
authors: Ping
authors: P
authors: Wu
authors: Ting-Xin
authors: TX
authors: Jiang
authors: Sung-Jan
authors: SJ
authors: Lin
authors: Chen-Yuan
authors: CY
authors: Dong
authors: Ang
authors: A
authors: Li
authors: Fon-Jou
authors: FJ
authors: Hsieh
authors: Randall B
authors: RB
authors: Widelitz
authors: Cheng Ming
authors: CM
authors: Chuong
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology; D002642:Chick Embryo; D015536:Down-Regulation / Q000235:genetics; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005241:Feathers / Q000196:embryology*; D015870:Gene Expression / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D018613:Microscopy, Confocal; D036641:Microscopy, Fluorescence, Multiphoton; D018715:Microscopy, Video; D009024:Morphogenesis / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D012867:Skin / Q000033:anatomy & histology / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D049490:Systems Biology / Q000379:methods*; D013623:Tail / Q000196:embryology / Q000378:metabolism; D059008:Time-Lapse Imaging; D046509:Tissue Culture Techniques; D015854:Up-Regulation / Q000235:genetics; D014921:Wings, Animal / Q000196:embryology / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins