Faculty

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Randall Bruce Widelitz, PhD
Associate Professor of Research Pathology
Pathology
HMR 2011 Zonal Ave Health Sciences Campus Los Angeles
+1 323 442 1158

Overview

When organs are damaged due to injury they can be repaired or regenerated. Repair produces scars which do not offer complete functionality. In contrast, regeneration restores complete functionality. We have been trying to understand why in some tissues, repair is the primary response and in others regeneration is the primary response to injury. In particular, we have been studying the role of adult progenitor cells in tissue regeneration using ectodermal organs (hairs, feathers, and teeth) as models. Our focus has been on molecular and cellular aspects stem cell activation and how cells are guided for proper morphogenesis.

Publications

Self-organization process in newborn skin organoid formation inspires strategy to restore hair regeneration of adult cells. Proc Natl Acad Sci U S A. 2017 Aug 22; 114(34):E7101-E7110. View in: PubMed

Diverse feather shape evolution enabled by coupling anisotropic signalling modules with self-organizing branching programme. Nat Commun. 2017 Jan 20; 8:ncomms14139. View in: PubMed

MicroCT Imaging on Living Alligator Teeth Reveals Natural Tooth Cycling. Methods Mol Biol. 2017; 1650:355-362. View in: PubMed

The Molecular Circuit Regulating Tooth Development in Crocodilians. J Dent Res. 2016 Dec; 95(13):1501-1510. View in: PubMed

Quorum sensing and other collective regenerative behavior in organ populations. Curr Opin Genet Dev. 2016 Oct; 40:138-143. View in: PubMed

The Modulatable Stem Cell Niche: Tissue Interactions during Hair and Feather Follicle Regeneration. J Mol Biol. 2016 Apr 10; 428(7):1423-40. View in: PubMed

Topographical mapping of a- and ß-keratins on developing chicken skin integuments: Functional interaction and evolutionary perspectives. Proc Natl Acad Sci U S A. 2015 Dec 08; 112(49):E6770-9. View in: PubMed

Proper BMP Signaling Levels Are Essential for 3D Assembly of Hepatic Cords from Hepatoblasts and Mesenchymal Cells. Dig Dis Sci. 2015 Dec; 60(12):3669-80. View in: PubMed

Roles of GasderminA3 in Catagen-Telogen Transition During Hair Cycling. J Invest Dermatol. 2015 Sep; 135(9):2162-2172. View in: PubMed

Deciphering principles of morphogenesis from temporal and spatial patterns on the integument. Dev Dyn. 2015 Aug; 244(8):905-20. View in: PubMed

Organ-level quorum sensing directs regeneration in hair stem cell populations. Cell. 2015 Apr 09; 161(2):277-90. View in: PubMed

Development, regeneration, and evolution of feathers. Annu Rev Anim Biosci. 2015; 3:169-95. View in: PubMed

SnapShot: Branching Morphogenesis. Cell. 2014 Aug 28; 158(5):1212-1212. e1. View in: PubMed

Genomic organization, transcriptomic analysis, and functional characterization of avian a- and ß-keratins in diverse feather forms. Genome Biol Evol. 2014 Aug 24; 6(9):2258-73. View in: PubMed

Regenerative hair waves in aging mice and extra-follicular modulators follistatin, dkk1, and sfrp4. J Invest Dermatol. 2014 Aug; 134(8):2086-2096. View in: PubMed

Modulating hair follicle size with Wnt10b/DKK1 during hair regeneration. Exp Dermatol. 2014 Jun; 23(6):407-13. View in: PubMed

Dkk2/Frzb in the dermal papillae regulates feather regeneration. Dev Biol. 2014 Mar 15; 387(2):167-78. View in: PubMed

Disrupted ectodermal organ morphogenesis in mice with a conditional histone deacetylase 1, 2 deletion in the epidermis. J Invest Dermatol. 2014 Jan; 134(1):24-32. View in: PubMed

Topology of feather melanocyte progenitor niche allows complex pigment patterns to emerge. Science. 2013 Jun 21; 340(6139):1442-5. View in: PubMed

Specialized stem cell niche enables repetitive renewal of alligator teeth. Proc Natl Acad Sci U S A. 2013 May 28; 110(22):E2009-18. View in: PubMed

Shaping organs by a wingless-int/Notch/nonmuscle myosin module which orients feather bud elongation. Proc Natl Acad Sci U S A. 2013 Apr 16; 110(16):E1452-61. View in: PubMed

Therapeutic strategy for hair regeneration: hair cycle activation, niche environment modulation, wound-induced follicle neogenesis, and stem cell engineering. Expert Opin Biol Ther. 2013 Mar; 13(3):377-91. View in: PubMed

Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation. Proc Natl Acad Sci U S A. 2013 Jan 22; 110(4):1351-6. View in: PubMed

Tuning Wnt signals for more or fewer hairs. J Invest Dermatol. 2013 Jan; 133(1):7-9. View in: PubMed

Module-based complexity formation: periodic patterning in feathers and hairs. Wiley Interdiscip Rev Dev Biol. 2013 Jan-Feb; 2(1):97-112. View in: PubMed

Sprouty/FGF signaling regulates the proximal-distal feather morphology and the size of dermal papillae. Dev Biol. 2012 Dec 01; 372(1):45-54. View in: PubMed

Progressive alopecia reveals decreasing stem cell activation probability during aging of mice with epidermal deletion of DNA methyltransferase 1. J Invest Dermatol. 2012 Dec; 132(12):2681-90. View in: PubMed

Physiological regeneration of skin appendages and implications for regenerative medicine. Physiology (Bethesda). 2012 Apr; 27(2):61-72. View in: PubMed

The chicken frizzle feather is due to an a-keratin (KRT75) mutation that causes a defective rachis. PLoS Genet. 2012; 8(7):e1002748. View in: PubMed

Roles of EphB3/ephrin-B1 in feather morphogenesis. Int J Dev Biol. 2012; 56(9):719-28. View in: PubMed

From buds to follicles: matrix metalloproteinases in developmental tissue remodeling during feather morphogenesis. Differentiation. 2011 Jun; 81(5):307-14. View in: PubMed

Self-organizing and stochastic behaviors during the regeneration of hair stem cells. Science. 2011 Apr 29; 332(6029):586-9. View in: PubMed

In search of the Golden Fleece: unraveling principles of morphogenesis by studying the integrative biology of skin appendages. Integr Biol (Camb). 2011 Apr; 3(4):388-407. View in: PubMed

Spots and stripes: pleomorphic patterning of stem cells via p-ERK-dependent cell chemotaxis shown by feather morphogenesis and mathematical simulation. Dev Biol. 2009 Oct 15; 334(2):369-82. View in: PubMed

The river of stem cells. Cell Stem Cell. 2009 Feb 06; 4(2):100-2. View in: PubMed

Analyses of regenerative wave patterns in adult hair follicle populations reveal macro-environmental regulation of stem cell activity. Int J Dev Biol. 2009; 53(5-6):857-68. View in: PubMed

Conversion of the nipple to hair-bearing epithelia by lowering bone morphogenetic protein pathway activity at the dermal-epidermal interface. Am J Pathol. 2008 Nov; 173(5):1339-48. View in: PubMed

Wnt signaling in skin organogenesis. Organogenesis. 2008 Apr; 4(2):123-33. View in: PubMed

Mammary glands and feathers: comparing two skin appendages which help define novel classes during vertebrate evolution. Semin Cell Dev Biol. 2007 Apr; 18(2):255-66. View in: PubMed

Molecular signaling in feather morphogenesis. Curr Opin Cell Biol. 2006 Dec; 18(6):730-41. View in: PubMed

Distinct mechanisms underlie pattern formation in the skin and skin appendages. Birth Defects Res C Embryo Today. 2006 Sep; 78(3):280-91. View in: PubMed

Morphoregulation of avian beaks: comparative mapping of growth zone activities and morphological evolution. Dev Dyn. 2006 May; 235(5):1400-12. View in: PubMed

Wnt3a gradient converts radial to bilateral feather symmetry via topological arrangement of epithelia. Proc Natl Acad Sci U S A. 2006 Jan 24; 103(4):951-5. View in: PubMed

Mapping stem cell activities in the feather follicle. Nature. 2005 Dec 15; 438(7070):1026-9. View in: PubMed

Wnt signaling through canonical and non-canonical pathways: recent progress. Growth Factors. 2005 Jun; 23(2):111-6. View in: PubMed

Rooster feathering, androgenic alopecia, and hormone-dependent tumor growth: what is in common? Differentiation. Rooster feathering, androgenic alopecia, and hormone-dependent tumor growth: what is in common? Differentiation. 2004 Dec; 72(9-10):474-88. View in: PubMed

Molecular shaping of the beak. Science. 2004 Sep 03; 305(5689):1465-6. View in: PubMed

Regulating the regulators: routing the Wnt-beta-catenin--Lef signals. J Invest Dermatol. 2004 Aug; 123(2):VIII-X. View in: PubMed

Sculpting skin appendages out of epidermal layers via temporally and spatially regulated apoptotic events. J Invest Dermatol. 2004 Jun; 122(6):1348-55. View in: PubMed

Distinct Wnt members regulate the hierarchical morphogenesis of skin regions (spinal tract) and individual feathers. Mech Dev. 2004 Feb; 121(2):157-71. View in: PubMed

Morphogenesis of chicken liver: identification of localized growth zones and the role of beta-catenin/Wnt in size regulation. Dev Biol. 2004 Feb 01; 266(1):109-22. View in: PubMed

The biology of feather follicles. Int J Dev Biol. 2004; 48(2-3):181-91. View in: PubMed

Evo-Devo of amniote integuments and appendages. Int J Dev Biol. 2004; 48(2-3):249-70. View in: PubMed

Integument pattern formation involves genetic and epigenetic controls: feather arrays simulated by digital hormone models. Int J Dev Biol. 2004; 48(2-3):117-35. View in: PubMed

Adaptation to the sky: Defining the feather with integument fossils from mesozoic China and experimental evidence from molecular laboratories. J Exp Zool B Mol Dev Evol. 2003 Aug 15; 298(1):42-56. View in: PubMed

Molecular biology of feather morphogenesis: a testable model for evo-devo research. J Exp Zool B Mol Dev Evol. 2003 Aug 15; 298(1):109-22. View in: PubMed

Shift of localized growth zones contributes to skin appendage morphogenesis: role of the Wnt/beta-catenin pathway. J Invest Dermatol. 2003 Jan; 120(1):20-6. View in: PubMed

The morphogenesis of feathers. Nature. 2002 Nov 21; 420(6913):308-12. View in: PubMed

Synergistic coactivator function by coactivator-associated arginine methyltransferase (CARM) 1 and beta-catenin with two different classes of DNA-binding transcriptional activators. J Biol Chem. 2002 Jul 19; 277(29):26031-5. View in: PubMed

Sonic hedgehog signaling pathway in vertebrate epithelial appendage morphogenesis: perspectives in development and evolution. Cell Mol Life Sci. 2000 Nov; 57(12):1672-81. View in: PubMed

Evo-devo of feathers and scales: building complex epithelial appendages. Curr Opin Genet Dev. 2000 Aug; 10(4):449-56. View in: PubMed

beta-catenin in epithelial morphogenesis: conversion of part of avian foot scales into feather buds with a mutated beta-catenin. Dev Biol. 2000 Mar 01; 219(1):98-114. View in: PubMed

Msx-2 and the regulation of organ size: epidermal thickness and hair length. J Investig Dermatol Symp Proc. 1999 Dec; 4(3):278-81. View in: PubMed

Early events in skin appendage formation: induction of epithelial placodes and condensation of dermal mesenchyme. J Investig Dermatol Symp Proc. 1999 Dec; 4(3):302-6. View in: PubMed

In vivo analysis of cancerous gene expression by RNA-polymerase chain reaction. Nucleic Acids Res. 1999 Dec 01; 27(23):4585-9. View in: PubMed

Self-organization of periodic patterns by dissociated feather mesenchymal cells and the regulation of size, number and spacing of primordia. Development. 1999 Nov; 126(22):4997-5009. View in: PubMed

Epidermal dysplasia and abnormal hair follicles in transgenic mice overexpressing homeobox gene MSX-2. J Invest Dermatol. 1999 Aug; 113(2):230-7. View in: PubMed

Wnt-7a in feather morphogenesis: involvement of anterior-posterior asymmetry and proximal-distal elongation demonstrated with an in vitro reconstitution model. Development. 1999 Jun; 126(12):2577-87. View in: PubMed

Local inhibitory action of BMPs and their relationships with activators in feather formation: implications for periodic patterning. Dev Biol. 1998 Apr 01; 196(1):11-23. View in: PubMed

Lineage and pluripotentiality of epithelial precursor cells in developing chicken skin. Biochem Cell Biol. 1998; 76(6):1069-77. View in: PubMed

Isolation and characterization of chicken beta-catenin. Gene. 1997 Sep 01; 196(1-2):201-7. View in: PubMed

Molecular histology in skin appendage morphogenesis. Microsc Res Tech. 1997 Aug 15; 38(4):452-65. View in: PubMed

FGF induces new feather buds from developing avian skin. J Invest Dermatol. 1996 Dec; 107(6):797-803. View in: PubMed

Early events during avian skin appendage regeneration: dependence on epithelial-mesenchymal interaction and order of molecular reappearance. J Invest Dermatol. 1996 Oct; 107(4):639-46. View in: PubMed

cDCC (chicken homologue to a gene deleted in colorectal carcinoma) is an epithelial adhesion molecule expressed in the basal cells and involved in epithelial-mesenchymal interaction. Dev Biol. 1994 Aug; 164(2):383-97. View in: PubMed

Adhesion molecules in skeletogenesis: II. Neural cell adhesion molecules mediate precartilaginous mesenchymal condensations and enhance chondrogenesis. J Cell Physiol. 1993 Aug; 156(2):399-411. View in: PubMed

Adhesion molecules and homeoproteins in the phenotypic determination of skin appendages. J Invest Dermatol. 1993 Jul; 101(1 Suppl):10S-15S. View in: PubMed

Roles of adhesion molecules NCAM and tenascin in limb skeletogenesis: analysis with antibody perturbation, exogenous gene expression, talpid mutants and activin stimulation. Prog Clin Biol Res. 1993; 383B:465-74. View in: PubMed

Replication-defective virus infection of feather buds produces a localized region of beta-galactosidase activity. Biochem Biophys Res Commun. 1992 Jul 31; 186(2):1020-4. View in: PubMed

Mechanism of skin morphogenesis. II. Retinoic acid modulates axis orientation and phenotypes of skin appendages. Development. 1992 Jul; 115(3):839-52. View in: PubMed

Accumulation of heat shock protein 70 RNA and its relationship to protein synthesis after heat shock in mammalian cells. Exp Cell Res. 1987 Feb; 168(2):539-45. View in: PubMed

Effects of cycloheximide on thermotolerance expression, heat shock protein synthesis, and heat shock protein mRNA accumulation in rat fibroblasts. Mol Cell Biol. 1986 Apr; 6(4):1088-94. View in: PubMed

Differential effects of lysosomotropic amines and polyamines on processing and biological activity of EGF. Exp Cell Res. 1984 Nov; 155(1):163-70. View in: PubMed

Dissociation of 68,000 Mr heat shock protein synthesis from thermotolerance expression in rat fibroblasts. Radiat Res. 1984 Aug; 99(2):433-7. View in: PubMed

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