title: Module-based complexity formation: periodic patterning in feathers and hairs.
abstract: Patterns describe order which emerges from homogeneity. Complex patterns on the integument are striking because of their visibility throughout an organism’s lifespan. Periodic patterning is an effective design because the ensemble of hair or feather follicles (modules) allows the generation of complexity, including regional variations and cyclic regeneration, giving the skin appendages a new lease on life. Spatial patterns include the arrangements of feathers and hairs in specific number, size, and spacing.We explorehowa field of equivalent progenitor cells can generate periodically arranged modules based on genetic information, physical–chemical rules and developmental timing. Reconstitution experiments suggest a competitive equilibrium regulated by activators/inhibitors involving Turing reaction-diffusion. Temporal patterns result from oscillating stem cell activities within each module (microenvironment regulation), reflected as growth (anagen) and resting (telogen) phases during the cycling of feather and hair follicles. Stimulating modules with activators initiates the spread of regenerative hair waves, while global inhibitors outside each module (macroenvironment) prevent this. Different wave patterns can be simulated by cellular automata principles. Hormonal status and seasonal changes can modulate appendage phenotypes, leading to ‘organ metamorphosis’, with multiple ectodermal organ phenotypes generated from the same precursors. We discuss potential novel evolutionary steps using this module-based complexity in several amniote integument organs, exemplified by the spectacular peacock feather pattern. We thus explore the application of the acquired knowledge of patterning in tissue engineering. New hair follicles can be generated after wounding. Hairs and feathers can be reconstituted through self-organization of dissociated progenitor cells.
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. cmchuong@usc.edu
authors.forename: Cheng-Ming
authors.initials: CM
authors.lastname: Chuong
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Yeh
authors.forename: Ting-Xin
authors.initials: TX
authors.lastname: Jiang
authors.forename: Randall
authors.initials: R
authors.lastname: Widelitz
mesh_terms: D000818:Animals; D019521:Body Patterning; D005241:Feathers / Q000502:physiology*; D006197:Hair / Q000502:physiology*; D034582:Integumentary System / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D023822:Tissue Engineering
references.citation: Mech Dev. 2004 Feb;121(2):157-71
references.pmid: 15037317
references.citation: Development. 1999 Jun;126(12):2577-87
references.pmid: 10331970
references.citation: Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10246-9
references.pmid: 8816784
references.citation: Naturwissenschaften. 2004 Jan;91(1):22-5
references.pmid: 14740099
references.citation: Tissue Eng Part C Methods. 2011 Apr;17(4):391-400
references.pmid: 21034159
references.citation: J Invest Dermatol. 2008 May;128(5):1071-80
references.pmid: 18094733
references.citation: J Invest Dermatol. 2003 Jan;120(1):36-47
references.pmid: 12535196
references.citation: Dev Dyn. 2007 Mar;236(3):755-68
references.pmid: 17279577
references.citation: Dev Biol. 2009 Oct 15;334(2):369-82
references.pmid: 19647731
references.citation: Int J Dev Biol. 2004;48(2-3):117-35
references.pmid: 15272377
references.citation: Int J Dev Biol. 2004;48(2-3):149-56
references.pmid: 15272379
references.citation: J Invest Dermatol. 2005 May;124(5):867-76
references.pmid: 15854024
references.citation: Philos Trans R Soc Lond B Biol Sci. 1981 Oct 7;295(1078):451-60
references.pmid: 6117905
references.citation: Bone. 1999 Jul;25(1):91-3
references.pmid: 10423029
references.citation: Differentiation. 2004 Dec;72(9-10):474-88
references.pmid: 15617560
references.citation: Dev Cell. 2001 Jul;1(1):13-25
references.pmid: 11703920
references.citation: J Exp Zool. 2002 Aug 15;294(2):160-76
references.pmid: 12210117
references.citation: Science. 2006 Dec 8;314(5805):1595-8
references.pmid: 17095659
references.citation: Bioessays. 2000 Aug;22(8):753-60
references.pmid: 10918306
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):951-5
references.pmid: 16418297
references.citation: Bull Math Biol. 1990;52(1-2):153-97; discussion 119-52
references.pmid: 2185858
references.citation: Dev Biol. 1998 Apr 1;196(1):11-23
references.pmid: 9527877
references.citation: Science. 2006 Dec 1;314(5804):1397-8
references.pmid: 17138885
references.citation: Int J Dev Biol. 2004;48(2-3):103-6
references.pmid: 15272375
references.citation: Nature. 2007 May 17;447(7142):265-6
references.pmid: 17507966
references.citation: Q Rev Biol. 2002 Sep;77(3):261-95
references.pmid: 12365352
references.citation: FASEB J. 2002 Dec;16(14):1967-9
references.pmid: 12397096
references.citation: Endocrinol Metab Clin North Am. 1991 Mar;20(1):1-14
references.pmid: 2029881
references.citation: Nature. 2002 Nov 21;420(6913):308-12
references.pmid: 12442169
references.citation: FASEB J. 2002 Jun;16(8):896-8
references.pmid: 12039872
references.citation: J Invest Dermatol. 1996 Dec;107(6):797-803
references.pmid: 8941663
references.citation: FASEB J. 2005 Oct;19(12):1710-2
references.pmid: 16030176
references.citation: Differentiation. 2011 Jun;81(5):307-14
references.pmid: 21497985
references.citation: Int J Dev Biol. 2009;53(5-6):673-81
references.pmid: 19557676
references.citation: Science. 2011 Apr 29;332(6029):586-9
references.pmid: 21527712
references.citation: Development. 1993 Sep;119(1):85-96
references.pmid: 8275866
references.citation: J Embryol Exp Morphol. 1983 Dec;78:83-125
references.pmid: 6663234
references.citation: Mech Dev. 1998 Mar;72(1-2):159-68
references.pmid: 9533960
references.citation: Nature. 2003 Jan 23;421(6921):335-40
references.pmid: 12540892
references.citation: Eur J Dermatol. 2001 Jul-Aug;11(4):315-20
references.pmid: 11399537
references.citation: Science. 2006 Dec 1;314(5804):1447-50
references.pmid: 17082421
references.citation: Development. 2008 Mar;135(6):1019-28
references.pmid: 18256193
references.citation: Trends Biochem Sci. 2003 Oct;28(10):518-21
references.pmid: 14559178
references.citation: Dev Biol. 2000 Mar 1;219(1):98-114
references.pmid: 10677258
references.citation: Cell. 2007 Jan 12;128(1):17-20
references.pmid: 17218249
references.citation: Mech Dev. 2000 Mar 1;91(1-2):351-4
references.pmid: 10704863
references.citation: Dev Dyn. 1996 Oct;207(2):157-70
references.pmid: 8906419
references.citation: Science. 2010 Sep 24;329(5999):1616-20
references.pmid: 20929839
references.citation: PLoS Biol. 2011 Mar;9(3):e1001028
references.pmid: 21423653
references.citation: J Invest Dermatol. 2004 Jun;122(6):1348-55
references.pmid: 15175023
references.citation: IMA J Math Appl Med Biol. 1992;9(4):249-67
references.pmid: 1302760
references.citation: Int J Dev Biol. 2009;53(5-6):653-8
references.pmid: 19557673
references.citation: Nature. 2007 May 17;447(7142):316-20
references.pmid: 17507982
references.citation: PLoS Genet. 2009 Jul;5(7):e1000573
references.pmid: 19629164
references.citation: J Theor Biol. 1991 Apr 7;149(3):339-60
references.pmid: 2062100
references.citation: Development. 2004 Aug;131(16):3955-66
references.pmid: 15269169
references.citation: J Cell Physiol. 2003 Jul;196(1):144-53
references.pmid: 12767050
references.citation: Dev Dyn. 2004 Dec;231(4):741-9
references.pmid: 15532057
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11734-9
references.pmid: 16087884
references.citation: Physiology (Bethesda). 2012 Apr;27(2):61-72
references.pmid: 22505663
references.citation: Gen Comp Endocrinol. 1987 Feb;65(2):212-5
references.pmid: 3817444
references.citation: Development. 2008 Aug;135(16):2797-805
references.pmid: 18635609
references.citation: Mech Dev. 2002 Jan;110(1-2):51-60
references.pmid: 11744368
references.citation: Development. 2005 Mar;132(5):863-72
references.pmid: 15673574
references.citation: Development. 1999 Aug;126(16):3509-21
references.pmid: 10409498
references.citation: Mech Dev. 2001 Feb;100(2):331-3
references.pmid: 11165492
references.citation: Dev Biol. 1998 Sep 1;201(1):1-12
references.pmid: 9733569
references.citation: Int J Dev Biol. 2004;48(2-3):181-91
references.pmid: 15272383
references.citation: PLoS Comput Biol. 2007 Apr 27;3(4):e76
references.pmid: 17465675
references.citation: Nat Protoc. 2008;3(5):799-810
references.pmid: 18451788
references.citation: Curr Opin Cell Biol. 2006 Dec;18(6):730-41
references.pmid: 17049829
references.citation: J Exp Zool B Mol Dev Evol. 2003 Aug 15;298(1):42-56
references.pmid: 12949768
references.citation: J Exp Zool B Mol Dev Evol. 2003 Aug 15;298(1):1-11
references.pmid: 12949766
references.citation: Nat Rev Mol Cell Biol. 2009 Mar;10(3):207-17
references.pmid: 19209183
references.citation: Dev Biol. 2007 May 1;305(1):232-45
references.pmid: 17362907
references.citation: Int J Dev Biol. 2004;48(2-3):249-70
references.pmid: 15272390
references.citation: Development. 1999 Nov;126(22):4997-5009
references.pmid: 10529418
references.citation: Cell Adh Migr. 2007 Jul-Sep;1(3):149-51
references.pmid: 19262137
references.citation: Development. 1998 Oct;125(19):3775-87
references.pmid: 9729486
references.citation: J Investig Dermatol Symp Proc. 2005 Dec;10(3):243-6
references.pmid: 16382674
references.citation: Development. 2008 Jun;135(12):2161-72
references.pmid: 18480165
references.citation: Dev Biol. 1984 Dec;106(2):406-13
references.pmid: 6209181
references.citation: Development. 2010 Dec;137(23):4091-9
references.pmid: 21062866
references.citation: J Invest Dermatol. 1995 May;104(5):711-9
references.pmid: 7537773