Skip to main content

Advertisement

SpringerLink
Log in

Deletion of the endothelin-A receptor gene within the developing mandible

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Signaling from the endothelin-A (Ednra) receptor is responsible for initiating multiple signaling pathways within neural crest cells (NCCs). Loss of this initiation is presumably the basis for the craniofacial defects observed in Ednra−/− embryos. However, it is not known whether continued Ednra signaling in NCC derivatives is required for subsequent development of the lower jaw. To address this question, mice containing loxP recombination sequences flanking a portion of the Ednra gene were bred with transgenic mice that express Cre recombinase under control of a Dlx5/6 enhancer element. We find that while Ednra gene inactivation within the mandibular arch of these Ednra conditional knockout embryos is detectable by embryonic day (E) 10.5, mandibular arch-specific gene expression is normal, as is overall mandible development. These results suggest that while Ednra receptor signaling is crucial for early NCC patterning, subsequent Ednra signaling is not essential for mandible bone development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Beverdam A, Merlo GR, Paleari L, Mantero S, Genova F, Barbieri O, Janvier P, Levi G (2002) Jaw transformation with gain of symmetry after Dlx5/Dlx6 inactivation: mirror of the past. Genesis 34:221–227

    Article  CAS  PubMed  Google Scholar 

  • Clouthier DE, Schilling TF (2004) Understanding endothelin-1 function during craniofacial development in the mouse and zebrafish. Birth Defects Res (Part C) 72:190–199

    Article  CAS  Google Scholar 

  • Clouthier DE, Hosoda K, Richardson JA, Williams SC, Yanagisawa H, Kuwaki T, Kumada M, Hammer RE, Yanagisawa M (1998) Cranial and cardiac neural crest defects in endothelin-A receptor-deficient mice. Development 125:813–824

    CAS  PubMed  Google Scholar 

  • Clouthier DE, Williams SC, Yanagisawa H, Wieduwilt M, Richardson JA, Yanagisawa M (2000) Signaling pathways crucial for craniofacial development revealed by endothelin-A receptor-deficient mice. Dev Biol 217:10–24

    Article  CAS  PubMed  Google Scholar 

  • Clouthier DE, Williams SC, Hammer RE, Richardson JA, Yanagisawa H (2003) Cell-autonomous and non-autonomous actions of endothelin-A receptor signaling in craniofacial and cardiovascular development. Dev Biol 261:506–519

    Article  CAS  PubMed  Google Scholar 

  • Couly GF, Creazzo TL, Bennaceur S, Vincent C, Le Douarin NM (2002) Interactions between Hox-negative cephalic neural crest cells and the foregut endoderm in patterning the facial skeleton in the vertebrate head. Development 129:1061–1073

    CAS  PubMed  Google Scholar 

  • Depew MJ, Liu JK, Long JE, Presley R, Meneses JJ, Pedersen RA, Rubenstein JL (1999) Dlx5 regulates regional development of the branchial arches and sensory capsules. Development 126:3831–3846

    CAS  PubMed  Google Scholar 

  • Ivey K, Tyson B, Ukidwe P, McFadden DG, Levi G, Olson EN, Srivastava D, Wilkie TM (2003) Gαq and Gα11 proteins mediate endothelin-1 signaling in neural crest-derived pharyngeal arch mesenchyme. Dev Biol 255:230–237

    Article  CAS  PubMed  Google Scholar 

  • Kedzierski RM, Grayburn PA, Kisanuki YY, Williams CS, Hammer RE, Richardson JA, Schneider MD, Yanagisawa M (2003) Cardiomyocyte-specific endothelin a receptor knockout mice have normal cardiac function and an unaltered hypertrophic response to angiotensin II and isoproterenol. Mol Cell Biol 23:8226–8232

    Article  CAS  PubMed  Google Scholar 

  • Kempf H, Linares C, Corvol P, Gasc JM (1998) Pharmacological inactivation of the endothelin type A receptor in the early chick embryo: a model of mispatterning of the branchial arch derivatives. Development 125:4931–4941

    CAS  PubMed  Google Scholar 

  • Kitano Y, Kurihara H, Kurihara Y, Maemura K, Ryo Y, Yazaki Y, Harii K (1998) Gene expression of bone matrix proteins and endothelin receptors in endothelin-1-deficient mice revealed by in situ hybridization. J Bone Miner Res 13:237–244

    CAS  PubMed  Google Scholar 

  • Kurihara Y, Kurihara H, Suzuki H, Kodama T, Maemura K, Nagai R, Oda H, Kuwaki T, Cao W-H, Kamada N et al (1994) Elevated blood pressure and craniofacial abnormalities in mice deficient in endothelin-1. Nature 368:703–710

    Article  CAS  PubMed  Google Scholar 

  • Kwan K-M (2002) Conditional alleles in mice: practical considerations for tissue-specific knockouts. Genesis 32:49–62

    Article  CAS  PubMed  Google Scholar 

  • Le Douarin NM, Ziller C, Couly GF (1993) Patterning of neural crest derivatives in the avian embryo: in vivo and in vitro studies. Dev Biol 159:24–49

    Article  PubMed  Google Scholar 

  • Lumsden A, Sprawson N, Graham A (1991) Segmental origin and migration of neural crest cells in the hindbrain region of the chick embryo. Development 113:1281–1291

    CAS  PubMed  Google Scholar 

  • McLeod MJ (1980) Differential staining of cartilage and bone in whole mouse fetuses by alcian blue and alizarin red S. Teratology 22:299–301

    CAS  PubMed  Google Scholar 

  • Miller CT, Schilling TF, Lee K-H, Parker J, Kimmel CB (2000) sucker encodes a zebrafish endothelin-1 required for ventral pharyngeal arch development. Development 127:3815–3838

    CAS  PubMed  Google Scholar 

  • Miyama K, Yamada G, Yamamoto TS, Takagi C, Miyado K, Sakai M (1999) A BMP-inducible gene, Dlx5, regulates osteoblast differentiation and mesoderm induction. Dev Biol 208:123–133

    Article  CAS  PubMed  Google Scholar 

  • Nagy A (2000) Cre recombinase: the universal reagent for genome tailoring. Genesis 26:99–109

    Article  CAS  PubMed  Google Scholar 

  • Noden DM (1983) The role of the neural crest in patterning of avian cranial skeletal, connective, and muscle tissues. Dev Biol 96:144–165

    CAS  PubMed  Google Scholar 

  • Ozeki H, Kurihara Y, Tonami K, Watatani K, Kurihara H (2004) Endothelin-1 regulates the dorsoventral branchial arch patterning in mice. Mech Dev 121:387–395

    Article  CAS  PubMed  Google Scholar 

  • Park BK, Sperber SM, Choudhury A, Ghanem N, Hatch GT, Sharpe PT, Thomas BL, Ekker M (2004) Intergenic enhancers with distinct activities regulate Dlx gene expression in the mesenchyme of the branchial arches. Dev Biol 268:532–545

    Article  CAS  PubMed  Google Scholar 

  • Robledo RF, Rajan L, Li X, Lufkin T (2002) The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development. Genes Dev 16:1089–1101

    Article  CAS  PubMed  Google Scholar 

  • Ruest L-B, Hammer RE, Yanagisawa M, Clouthier DE (2003) Dlx5/6-enhancer directed expression of Cre recombinase in the pharyngeal arches and brain. Genesis 37:188–194

    Article  CAS  PubMed  Google Scholar 

  • Ruest L-B, Xiang X, Lim KC, Levi G, Clouthier DE (2004) Endothelin-A receptor-dependent and independent signaling pathways in establishing mandibular identity. Development 131:4413–4423

    Article  PubMed  Google Scholar 

  • Schneider RA, Helms JA (2003) The cellular and molecular origins of beak morphology. Science 299:565–568

    Article  CAS  PubMed  Google Scholar 

  • Serbedzija GN, Bronner-Fraser M, Fraser SE (1992) Vital dye analysis of cranial neural crest cell migration in the mouse embryo. Development 116:297–307

    CAS  PubMed  Google Scholar 

  • Spence S, Anderson C, Cukierski M, Patrick D (1999) Teratogenic effects of the endothelin receptor antagonist L-753,037 in the rat. Reprod Toxicol 13:15–29

    Article  CAS  PubMed  Google Scholar 

  • Srivastava D, Thomas T, Lin Q, Kirby ML, Brown D, Olson EN (1997) Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND. Nat Genet 16:154–160

    Article  CAS  PubMed  Google Scholar 

  • Stern PH, Tatrai A, Semler DE, Lee SK, Lakatos P, Strieleman PJ, Tarjan G, Sander JL (1995) Endothelin receptors, second messengers, and actions in bone. J Nutr 125:2028S–2032S

    CAS  PubMed  Google Scholar 

  • Suzuki A, Shinoda J, Watanabe-Tomita Y, Ozaki N, Oiso Y, Kozawa O (1997) ETA receptor mediates the signaling of endothelin-1 in osteoblast-like cells. Bone 21:143–146

    Article  CAS  PubMed  Google Scholar 

  • Thomas T, Kurihara H, Yamagishi H, Kurihara Y, Yazaki Y, Olson EN, Srivastava D (1998) A signaling cascade involving endothelin-1, dHAND and Msx1 regulates development of neural-crest-derived branchial arch mesenchyme. Development 125:3005–3014

    CAS  PubMed  Google Scholar 

  • Trainor PA, Ariza-McNaughton L, Krumlauf R (2002) Role of the isthmus and FGFs in resolving the paradox of neural crest plasticity and prepatterning. Science 295:1288–1291

    Article  CAS  PubMed  Google Scholar 

  • Tucker SA, Yamada G, Grigoriou M, Pachnis V, Sharpe PT (1999) Fgf-8 determines rostral-caudal polarity in the first branchial arch. Development 126:51–61

    CAS  PubMed  Google Scholar 

  • Yanagisawa H, Hammer RE, Richardson JA, Williams SC, Clouthier DE, Yanagisawa M (1998) Role of endothelin-1/endothelin-A receptor-mediated signaling pathway in the aortic arch patterning in mice. J Clin Invest 102:22–33

    CAS  PubMed  Google Scholar 

  • Yin JJ, Mohammad KS, Kokonen SM, Harris S, Wu-Wong JR, Wessale JL, Padley RJ, Garrett IR, Chirgwin JM, Guise TA (2003) A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases. Proc Natl Acad Sci USA 100:10954–10959

    Google Scholar 

Download references

Acknowledgements

The authors would like to thank Shelley Dixon and Tinisha Taylor for technical assistance. M.Y. is an investigator of the Howard Hughes Medical Institute. R.M.K is a trainee in the Medical Scientist Training Program at the University of Texas Southwestern Medical Center at Dallas. D.E.C. is a recipient of a Career Development Award from the NIDCR/NIH.

Author information

Authors and Affiliations

  1. Department of Molecular, Cellular and Craniofacial Biology and the Birth Defects Center, University of Louisville, Louisville, KY, 40292, USA

    Louis-Bruno Ruest & David E. Clouthier

  2. Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Rafal Kedzierski & Masashi Yanagisawa

  3. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Masashi Yanagisawa

Authors
  1. Louis-Bruno Ruest
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rafal Kedzierski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masashi Yanagisawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David E. Clouthier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David E. Clouthier.

Additional information

This work was supported in part by grants from the National Institutes of Health and the American Heart Association to D.E.C.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ruest, LB., Kedzierski, R., Yanagisawa, M. et al. Deletion of the endothelin-A receptor gene within the developing mandible. Cell Tissue Res 319, 447–453 (2005). https://doi.org/10.1007/s00441-004-0988-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-004-0988-1

Keywords

Search

Navigation