NFIA and GATA3 are crucial regulators of embryonic articular cartilage differentiation

ABSTRACT During appendicular skeletal development, the bi-potential cartilage anlagen gives rise to transient cartilage, which is eventually replaced by bone, and to articular cartilage that caps the ends of individual skeletal elements. While the molecular mechanism that regulates transient cartilage differentiation is relatively well understood, the mechanism of articular cartilage differentiation has only begun to be unraveled. Furthermore, the molecules that coordinate the articular and transient cartilage differentiation processes are poorly understood. Here, we have characterized in chick the regulatory roles of two transcription factors, NFIA and GATA3, in articular cartilage differentiation, maintenance and the coordinated differentiation of articular and transient cartilage. Both NFIA and GATA3 block hypertrophic differentiation. Our results suggest that NFIA is not sufficient but necessary for articular cartilage differentiation. Ectopic activation of GATA3 promotes articular cartilage differentiation, whereas inhibition of GATA3 activity promotes transient cartilage differentiation at the expense of articular cartilage. We propose a novel transcriptional circuitry involved in embryonic articular cartilage differentiation, maintenance and its crosstalk with the transient cartilage differentiation program. Summary: Chicken NFIA prevents hypertrophic differentiation in the interzone/articular region, whereas GATA3 activates articular cartilage-specific gene expression in concert with other transcription factors, possibly OSR1/2, c-JUN and Wnts.

[1]  C. Perrault,et al.  Sleeping Beauty , 2017, Beginning with O.

[2]  N. Speck,et al.  Articular Cartilage Endurance and Resistance to Osteoarthritic Changes Require Transcription Factor Erg , 2015, Arthritis & rheumatology.

[3]  R. Harland,et al.  Precise spatial restriction of BMP signaling is essential for articular cartilage differentiation , 2015, Development.

[4]  Melissa J. Davis,et al.  Sleeping Beauty mutagenesis in a mouse medulloblastoma model defines networks that discriminate between human molecular subgroups , 2013, Proceedings of the National Academy of Sciences.

[5]  C. Tabin,et al.  c-Jun is required for the specification of joint cell fates. , 2013, Genes & development.

[6]  Jun Wang,et al.  Bmp signaling regulates a dose-dependent transcriptional program to control facial skeletal development , 2012, Development.

[7]  A. Pitsillides,et al.  Cartilage biology in osteoarthritis—lessons from developmental biology , 2011, Nature Reviews Rheumatology.

[8]  C. Tabin,et al.  Promotion of avian endothelial cell differentiation by GATA transcription factors. , 2011, Developmental biology.

[9]  Han Liu,et al.  The zinc finger transcription factors Osr1 and Osr2 control synovial joint formation. , 2011, Developmental biology.

[10]  G. Daley,et al.  All-Trans Retinoic Acid Directs Urothelial Specification of Murine Embryonic Stem Cells via GATA4/6 Signaling Mechanisms , 2010, PloS one.

[11]  M. Bouchard,et al.  Gata3 Acts Downstream of β-Catenin Signaling to Prevent Ectopic Metanephric Kidney Induction , 2008, PLoS genetics.

[12]  T. Ogura,et al.  Congenic method in the chick limb buds by electroporation , 2008, Development, growth & differentiation.

[13]  D. Kingsley,et al.  Synovial Joint Formation during Mouse Limb Skeletogenesis , 2007, Annals of the New York Academy of Sciences.

[14]  Takashi Nakamura,et al.  Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis. , 2007, Developmental biology.

[15]  David J. Anderson,et al.  The Transcription Factor NFIA Controls the Onset of Gliogenesis in the Developing Spinal Cord , 2006, Neuron.

[16]  Zena Werb,et al.  GATA-3 Maintains the Differentiation of the Luminal Cell Fate in the Mammary Gland , 2006, Cell.

[17]  C. Hartmann,et al.  Role of canonical Wnt-signalling in joint formation. , 2006, European cells & materials.

[18]  C. Hartmann,et al.  Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis , 2006, Development.

[19]  S. Schneider,et al.  Gli3 acts as a repressor downstream of Ihh in regulating two distinct steps of chondrocyte differentiation , 2005, Development.

[20]  Masahiro Iwamoto,et al.  Mechanisms of synovial joint and articular cartilage formation: recent advances, but many lingering mysteries. , 2005, Birth defects research. Part C, Embryo today : reviews.

[21]  C. Tabin,et al.  The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate , 2005, Nature Cell Biology.

[22]  L. Topol,et al.  Wnt/β-catenin signaling is sufficient and necessary for synovial joint formation , 2004 .

[23]  H. Kronenberg,et al.  Developmental regulation of the growth plate , 2003, Nature.

[24]  C. Archer,et al.  Development of synovial joints. , 2003, Birth defects research. Part C, Embryo today : reviews.

[25]  E. Wagner,et al.  Reaching a genetic and molecular understanding of skeletal development. , 2002, Developmental cell.

[26]  J. Rosenbloom,et al.  The role of ERG (ets related gene) in cartilage development. , 2001, Osteoarthritis and cartilage.

[27]  Christine Hartmann,et al.  Wnt-14 Plays a Pivotal Role in Inducing Synovial Joint Formation in the Developing Appendicular Skeleton , 2001, Cell.

[28]  J. Rosenbloom,et al.  Transcription Factor Erg Variants and Functional Diversification of Chondrocytes during Limb Long Bone Development , 2000, The Journal of cell biology.

[29]  R. Gronostajski,et al.  Disruption of the murine nuclear factor I-A gene (Nfia) results in perinatal lethality, hydrocephalus, and agenesis of the corpus callosum. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[30]  A. McMahon,et al.  Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation. , 1999, Genes & development.

[31]  D. Kingsley,et al.  GDF5 coordinates bone and joint formation during digit development. , 1999, Developmental biology.

[32]  Richard R. Behringer,et al.  Sox9 is required for cartilage formation , 1999, Nature Genetics.

[33]  F. Luyten,et al.  Mechanisms of GDF-5 action during skeletal development. , 1999, Development.

[34]  A. Economides,et al.  Expression and function of Gdf-5 during digit skeletogenesis in the embryonic chick leg bud. , 1999, Developmental biology.

[35]  F. Luyten,et al.  Role of CDMP-1 in Skeletal Morphogenesis: Promotion of Mesenchymal Cell Recruitment and Chondrocyte Differentiation , 1999, The Journal of cell biology.

[36]  P. Vogt,et al.  The DF-1 chicken fibroblast cell line: transformation induced by diverse oncogenes and cell death resulting from infection by avian leukosis viruses. , 1998, Virology.

[37]  C. Tabin,et al.  Targeted gene misexpression in chick limb buds using avian replication-competent retroviruses. , 1998, Methods.

[38]  Clifford J. Tabin,et al.  Regulation of Rate of Cartilage Differentiation by Indian Hedgehog and PTH-Related Protein , 1996, Science.

[39]  B. Lanske,et al.  PTH/PTHrP Receptor in Early Development and Indian Hedgehog--Regulated Bone Growth , 1996, Science.

[40]  James Douglas Engel,et al.  Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis , 1995, Nature Genetics.

[41]  Y. Gañán,et al.  Modification of the phalangeal pattern of the digits in the chick embryo leg bud by local microinjection of RA, staurosporin and TGF β's , 1993, Anatomy and Embryology.

[42]  Simon,et al.  Mouse GATA-4: a retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart , 1993, Molecular and cellular biology.

[43]  William M. Potts,et al.  Epitope mapping of monoclonal antibodies to gag protein p19 of avian sarcoma and leukaemia viruses. , 1987, The Journal of general virology.

[44]  N Holder,et al.  An experimental investigation into the early development of the chick elbow joint. , 1977, Journal of embryology and experimental morphology.

[45]  V. Hamburger,et al.  A series of normal stages in the development of the chick embryo , 1951, Journal of morphology.

[46]  K. Azad,et al.  A comprehensive mRNA expression analysis of developing chicken articular cartilage. , 2016, Gene expression patterns : GEP.

[47]  Xizhi Guo,et al.  Wnt/beta-catenin signaling is sufficient and necessary for synovial joint formation. , 2004, Genes & development.

[48]  윤호주.  전사인자(transcription factor)와 기관지천식 , 1999 .

[49]  P. Alberch,et al.  A morphogenetic approach to the origin and basic organization of the tetrapod limb , 1986 .