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PMID: 9707582 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Evidence for regulation of cartilage differentiation by the homeobox gene Hoxc-8.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 17 ·1998-08-18 ·Pages 9956-61

Yueh YG, Gardner DP, Kappen C

Abstract

Homeobox genes of the Hox class are required for proper patterning of skeletal elements, but how they regulate the differentiation of specific tissues is unclear. We show here that overexpression of a Hoxc-8 transgene causes cartilage defects whose severity depends on transgene dosage. The abnormal cartilage is characterized by an accumulation of proliferating chondrocytes and reduced maturation. Since Hoxc-8 is normally expressed in chondrocytes, these results suggest that Hoxc-8 continues to regulate skeletal development well beyond pattern formation in a tissue-specific manner, presumably by controlling the progression of cells along the chondrocyte differentiation pathway. The comparison to Hoxd-4 and Isl-1 indicates that this role in chondrogenesis is specific to proteins of the Hox class. Their capacity for regulation of cartilage differentiation suggests that Hox genes could also be involved in human chondrodysplasias or other cartilage disorders.

MeSH Terms
Animals Cartilage/abnormalities,embryology,metabolism Cell Differentiation/genetics Chondrocytes/cytology,metabolism Crosses, Genetic Exostoses, Multiple Hereditary/embryology,genetics Female Gene Expression Regulation, Developmental Genes, Homeobox Genotype Homeodomain Proteins/genetics Humans Male Mice Mice, Transgenic Models, Biological Phenotype Pregnancy
Chemicals
HOXC8 protein, human Homeodomain Proteins Hoxc8 protein, mouse
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Yueh Y G
Department of Biochemistry and Molecular Biology, Samuel C. Johnson Medical Research Center, Mayo Clinic Scottsdale, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA.
Gardner D P
Kappen C
References (38)
38 references, click to expand
  1. Biochemical evidence that patched is the Hedgehog receptor.
    Nature. 1996 Nov 14;384(6605):176-9 PMID: 8906794
  2. The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog.
    Nature. 1996 Nov 14;384(6605):129-34 PMID: 8906787
  3. Genetic interactions of Hox genes in limb development: learning from compound mutants.
    Curr Opin Genet Dev. 1997 Aug;7(4):481-7 PMID: 9309178
  4. Hoxd-12 differentially affects preaxial and postaxial chondrogenic branches in the limb and regulates Sonic hedgehog in a positive feedback loop.
    Development. 1997 Nov;124(22):4523-36 PMID: 9409670
  5. Primary structure and developmental expression pattern of Hox 3.1, a member of the murine Hox 3 homeobox gene cluster.
    EMBO J. 1988 May;7(5):1329-36 PMID: 2900757
  6. Multiplex gene regulation: a two-tiered approach to transgene regulation in transgenic mice.
    Proc Natl Acad Sci U S A. 1989 Jul;86(14):5473-7 PMID: 2568635
  7. Insulin gene enhancer binding protein Isl-1 is a member of a novel class of proteins containing both a homeo- and a Cys-His domain.
    Nature. 1990 Apr 26;344(6269):879-82 PMID: 1691825
  8. Variations of cervical vertebrae after expression of a Hox-1.1 transgene in mice.
    Cell. 1990 Apr 20;61(2):301-8 PMID: 1970515
  9. Evidence for positive and negative regulation of the Hox-3.1 gene.
    Proc Natl Acad Sci U S A. 1990 Nov;87(21):8462-6 PMID: 1978325
  10. Analysis of regulatory genes using the transgenic mouse system.
    Biotechnology. 1991;16:135-52 PMID: 1672506
  11. Alternatively spliced type II procollagen mRNAs define distinct populations of cells during vertebral development: differential expression of the amino-propeptide.
    J Cell Biol. 1991 Sep;114(6):1307-19 PMID: 1894696
  12. Homeosis in the mouse induced by a null mutation in the Hox-3.1 gene.
    Cell. 1992 Apr 17;69(2):251-64 PMID: 1348969
  13. Identification and characterization of a novel, evolutionarily conserved gene disrupted by the murine H beta 58 embryonic lethal transgene insertion.
    Development. 1992 May;115(1):277-88 PMID: 1638986
  14. Homeotic transformation of the occipital bones of the skull by ectopic expression of a homeobox gene.
    Nature. 1992 Oct 29;359(6398):835-41 PMID: 1359423
  15. Homeotic transformations in the mouse induced by overexpression of a human Hox3.3 transgene.
    Cell. 1992 Dec 11;71(6):901-10 PMID: 1360874
  16. Altering the boundaries of Hox3.1 expression: evidence for antipodal gene regulation.
    Cell. 1992 Dec 11;71(6):911-23 PMID: 1360875
  17. Assembly of cartilage collagen fibrils is disrupted by overexpression of normal type II collagen in transgenic mice.
    Proc Natl Acad Sci U S A. 1993 May 1;90(9):3825-9 PMID: 8483900
  18. Hox genes in vertebrate development.
    Cell. 1994 Jul 29;78(2):191-201 PMID: 7913880
  19. Ectopic expression of Hoxb-8 causes duplication of the ZPA in the forelimb and homeotic transformation of axial structures.
    Cell. 1994 Aug 26;78(4):589-601 PMID: 7915198
  20. Altering the spatial determinations in the mouse embryos by manipulating the Hox genes.
    C R Acad Sci III. 1993 Sep;316(9):1009-24 PMID: 7915631
  21. In situ expression of collagen and proteoglycan genes in notochord and during skeletal development and growth.
    Microsc Res Tech. 1994 Aug 15;28(6):470-82 PMID: 7949393
  22. Mutations in paralogous Hox genes result in overlapping homeotic transformations of the axial skeleton: evidence for unique and redundant function.
    Dev Biol. 1995 May;169(1):359-72 PMID: 7750651
  23. Compound mutants for the paralogous hoxa-4, hoxb-4, and hoxd-4 genes show more complete homeotic transformations and a dose-dependent increase in the number of vertebrae transformed.
    Genes Dev. 1995 Jul 1;9(13):1667-77 PMID: 7628700
  24. Vertebrate Hox genes and proliferation: an alternative pathway to homeosis?
    Curr Opin Genet Dev. 1995 Aug;5(4):525-8 PMID: 7580146
  25. Regulation of Hoxc-8 during mouse embryonic development: identification and characterization of critical elements involved in early neural tube expression.
    Development. 1995 Dec;121(12):4339-47 PMID: 8575334
  26. Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation.
    Cell. 1996 Jan 26;84(2):309-20 PMID: 8565076
  27. Spatial and temporal regulation of a lacZ reporter transgene in a binary transgenic mouse system.
    Transgenic Res. 1996 Jan;5(1):37-48 PMID: 8589738
  28. Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog.
    Genes Dev. 1996 Feb 1;10(3):301-12 PMID: 8595881
  29. Functional cooperation between the non-paralogous genes Hoxa-10 and Hoxd-11 in the developing forelimb and axial skeleton.
    Development. 1996 Feb;122(2):449-60 PMID: 8625796
  30. A mutational analysis of the 5' HoxD genes: dissection of genetic interactions during limb development in the mouse.
    Development. 1996 Apr;122(4):1175-85 PMID: 8620844
  31. Function of homeobox genes in skeletal development.
    Ann N Y Acad Sci. 1996 Jun 8;785:34-7 PMID: 8702174
  32. Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein.
    Science. 1996 Aug 2;273(5275):613-22 PMID: 8662546
  33. Functional specificity of Hoxa-4 in vertebral patterning lies outside of the homeodomain.
    Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9636-40 PMID: 8790382
  34. Programmed cell death of chondrocytes and aberrant chondrogenesis in mice homozygous for parathyroid hormone-related peptide gene deletion.
    Endocrinology. 1996 Nov;137(11):5055-67 PMID: 8895380
  35. Dual roles for patched in sequestering and transducing Hedgehog.
    Cell. 1996 Nov 1;87(3):553-63 PMID: 8898207
  36. Hoxa-13 and Hoxd-13 play a crucial role in the patterning of the limb autopod.
    Development. 1996 Oct;122(10):2997-3011 PMID: 8898214
  37. Synpolydactyly in mice with a targeted deficiency in the HoxD complex.
    Nature. 1996 Nov 7;384(6604):69-71 PMID: 8900279
  38. Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells.
    Nature. 1997 Jan 16;385(6613):257-60 PMID: 9000074
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.17.9956
Published
1998-08-18
Pages
9956-61
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC21443
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.95.17.9956 PMC Full Text View journal details
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