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Transgenic Research

, Volume 20, Issue 1, pp 23–28 | Cite as

Spatial p21 expression profile in the mid-term mouse embryo

  • Douglas B. VaseyEmail author
  • C. Roland Wolf
  • Ken Brown
  • C. Bruce A. Whitelaw
Original Paper

Abstract

Throughout development cells make the decision to proliferate, arrest or die. Control of this process is essential for normal development, with unrestrained cell proliferation and cell death underling the origin and progression of disease. The cell-cycle is tightly regulated by a number of factors including the cyclin-dependent kinase inhibitor 1A (Cdkn1a), termed p21 (or Cip1 or WAF1). p21 acts as a negative regulator of cell-cycle progression by binding and inhibiting complexes formed between the cyclin-dependent kinases and their catalytic partners the cyclins. In this report we identify the temporal spatial expression profile of p21 in the developing mid-term mouse embryo using a p21-LacZ reporter mouse line. Expression of p21 was restricted to specific regions with a correspondence to both areas of terminal differentiation and active remodelling. A complex temporal and spatial relationship between p21 expression and regions of apoptosis was evident. A protective role with regard to apoptosis for p21 is proposed.

Keywords

Apoptosis Cell-cycle Interdigit zone OPT LacZ p21 

Notes

Acknowledgments

We are grateful to the animal care staff for their assistance in this project. This work was funded by the BBSRC through a CASE award with CXR Biosciences LTD to DV and ISPG support to CBAW.

Supplementary material

11248_2010_9385_MOESM1_ESM.tif (540 kb)
Supplementary Fig. 1 LacZ staining in p21-LacZ and non transgenic 14.5 dpc embryos. LacZ staining was carried out on 14.5 dpc embryos of p21-LacZ and non transgenic CBA/C57BL/6 genetic background. Staining was detected in various regions of the p21-LacZ embryo while no staining was detected in the non transgenic embryo, n = 3 (TIFF 539 kb)

Supplemental Video S2 (MPG 4322 kb)

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Supplemental Video S7 (MPG 15670 kb)

References

  1. Boulaire J, Fotedar A, Fotedar A, Fotedar R (2000) The functions of the cdk-cyclin kinase inhibitor p21WAF1. Pathol Biol (Paris) 48.3:190–202Google Scholar
  2. Buckingham M (2001) Skeletal muscle formation in vertebrates. Curr Opin Genet Dev 11(4):440–448CrossRefPubMedGoogle Scholar
  3. Capocefalo A et al (2009) p21(Waf1/Cip1) as a molecular sensor for BoHV-4 replication. J Virol Methods 161(2):308–311CrossRefPubMedGoogle Scholar
  4. Cecconi F, Gruss P (2001) Apaf1 in developmental apoptosis and cancer: how many ways to die? Cell Mol Life Sci 58(11):1688–1697CrossRefPubMedGoogle Scholar
  5. Cinnamon Y, Kahane N, Kalcheim C (1999) Characterization of the early development of specific hypaxial muscles from the ventrolateral myotome. Development 126(19):4305–4315PubMedGoogle Scholar
  6. Dietrich S et al (1998) Specification of the hypaxial musculature. Development 125(12):2235–2249PubMedGoogle Scholar
  7. Donner AJ et al (2007) Stimulus-specific transcriptional regulation within the p53 network. Cell Cycle 6(21):2594–2598CrossRefPubMedGoogle Scholar
  8. Fallon JF, Saunders JW Jr (1968) In vitro analysis of the control of cell death in a zone of prospective necrosis from the chick wing bud. Dev Biol 18(6):553–570CrossRefPubMedGoogle Scholar
  9. Gartel AL (2006) Inducer and inhibitor: “antagonistic duality of p21 in differentiation.”. Leuk Res 30(10):1215–1216CrossRefPubMedGoogle Scholar
  10. Gartel AL, Tyner AL (2002) The role of the cyclin-dependent kinase inhibitor p21 in apoptosis. Mol Cancer Ther 1(8):639–649PubMedGoogle Scholar
  11. Gong S et al (2003) A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature 425(6961):917–925CrossRefPubMedGoogle Scholar
  12. Macleod KF et al (1995) p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage. Genes Dev 9(8):935–944CrossRefPubMedGoogle Scholar
  13. Parker SB et al (1995) p53-independent expression of p21Cip1 in muscle and other terminally differentiating cells. Science 267(5200):1024–1027CrossRefPubMedGoogle Scholar
  14. Saunders JW Jr (1966) Death in embryonic systems. Science 154(749):604–612CrossRefPubMedGoogle Scholar
  15. Sharpe J et al (2002) Optical projection tomography as a tool for 3D microscopy and gene expression studies. Science 296(5567):541–545CrossRefPubMedGoogle Scholar
  16. Sporle R (2001) Epaxial-adaxial-hypaxial regionalisation of the vertebrate somite: evidence for a somitic organiser and a mirror-image duplication. Dev Genes Evol 211(4):198–217CrossRefPubMedGoogle Scholar
  17. van Kleffens M et al (1998) mRNA expression patterns of the IGF system during mouse limb bud development, determined by whole mount in situ hybridization. Mol Cell Endocrinol 138(1–2):151–161CrossRefPubMedGoogle Scholar
  18. Vasey DB et al (2008) p21-LacZ reporter mice reflect p53-dependent toxic insult. Toxicol Appl Pharmacol 227(3):440–450CrossRefPubMedGoogle Scholar
  19. Zuzarte-Luis V, Hurle JM (2005) Programmed cell death in the embryonic vertebrate limb. Semin Cell Dev Biol 16(2):261–269CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Douglas B. Vasey
    • 1
    • 2
    Email author
  • C. Roland Wolf
    • 2
    • 3
  • Ken Brown
    • 3
  • C. Bruce A. Whitelaw
    • 1
  1. 1.Division of Developmental Biology, The Roslin Institute and Royal (Dick), School of Veterinary StudiesUniversity of EdinburghRoslinUK
  2. 2.Biomedical Research Institute, Ninewells Hospital and Medical SchoolUniversity of DundeeDundeeUK
  3. 3.CXR Biosciences LimitedDundeeUK

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