Heart and extra-embryonic mesodermal defects in mouse embryos lacking the bHLH transcription factor Hand1 (original) (raw)

Nature Genetics volume 18, pages 266–270 (1998)Cite this article

Abstract

The basic helix-loop-helix (bHLH) transcription factors, Handl and Hand2 (refs 1,2), also called eHand/Hxt/Thing1 and dHand/Hed/Thing2 (refs 3,4), respectively, are expressed in the heart and certain neural-crest derivatives during embryogenesis. In addition, Handl is expressed in extraembryonic membranes, whereas Hand2 is expressed in the deciduum. Previous studies have demonstrated that Hand2 is required for formation of the right ventricle of the heart and the aortic arch arteries5. We have generated a germline mutation in the mouse Handl gene by replacing the first coding exon with a β-galactosidase reporter gene. Embryos homozygous for the Hand1 null allele died between embryonic days 8.5 and 9.5 and exhibited yolk sac abnormalities due to a deficiency in extraembryonic mesoderm. Heart development was also perturbed and did not progress beyond the cardiac-looping stage. Our results demonstrate important roles for Handl in extraembryonic mesodermal and heart development.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 12 print issues and online access

$209.00 per year

only $17.42 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Cserjesi, P., Brown, D., Lyons, G.E. & Olson, E.N. Expression of the novel basic helix-loop-helix gene eHAND in neural crest derivatives and extraembryonic membranes during mouse development. Dev. Biol. 170, 664–678 (1995).
    Article CAS PubMed Google Scholar
  2. Srivastava, D., Cserjesi, P. & Olson, E.N. A subclass of bHLH proteins required for cardiac morphogenesis. Science 270, 1995–1999 (1995).
    Article CAS PubMed Google Scholar
  3. Cross, J.C. et al. Hxt encodes a basic helix-loop-helix transcription factor that regulates trophoblast cell development. Development 121, 2513–2523 (1995).
    CAS PubMed Google Scholar
  4. Hollenberg, S.M., Sternglanz, R., Cheng, P.F. & Weintraub, H. Identification of a new family of tissue-specific basic helix-loop-helix proteins with a two-hybrid system. Mol. Cell. Biol. 15, 3813–3822 (1995).
    Article CAS PubMed PubMed Central Google Scholar
  5. Srivastava, D. et al. Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND. Nature Genet. 16, 154–160 (1997).
    Article CAS PubMed Google Scholar
  6. Olson, E.N. & Srivastava, D. Molecular pathways controlling heart development. Science 272, 671–676 (1996).
    Article CAS PubMed Google Scholar
  7. Le Douarin, N.M.C., & Couly, G. Patterns of neural crest derivatives in the avian embryos: In vivo and in vitro studies. Dev. Biol. 159, 24–49 (1993).
    Article CAS PubMed Google Scholar
  8. Simeone, A. et al. A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo. EMBO J. 12, 2735–2747 (1993).
    Article CAS PubMed PubMed Central Google Scholar
  9. Ruiz i Altaba, A., Prezioso, V.R., Darnell, J.E. & Jessell, T.M. Sequential expression of HNF-3 beta and HNF-3 alpha by embryonic organizing centers: the dorsal lip/node, notochord and floor plate. Mech. Dev. 44, 91–108 (1993).
    Article CAS PubMed Google Scholar
  10. O'Brien, T.X., Lee, K.J. & Chien, K.R. Positional specification of ventricular myosin light chain 2 expression in the primitive murine heart tube. Proc. Natl. Acad. Sci. USA 90, 5157–5161 (1993).
    Article CAS PubMed PubMed Central Google Scholar
  11. Biben, C. & Harvey, R.P. Homeodomain factor Nkx2-5 controls left/right asymmetric expression of bHLH gene eHAND during murine heart development. Genes Dev. 11, 1357–1369 (1997).
    Article CAS PubMed Google Scholar
  12. Martin, J.F., Bradley, A. & Olson, E.N. The paired-like homeobox gene mHox is required for early events of skeletogenesis in multiple lineages. Genes Dev. 9, 1237–1249 (1995).
    Article CAS PubMed Google Scholar
  13. Cheng, T.C., Wallace, M.C., Merlie, J.P. & Olson, E.N. Separable regulatory elements governing myogenin transcription in mouse embryogenesis. Science 261, 215–218 (1993).
    Article CAS PubMed Google Scholar
  14. Barth, J. & Ivarie, R. Polyvinyl alcohol enhances detection of low abundance transcripts in early stage quail embryos in a non-radioactive whole mount in situ hybridization technique. Biotechniques 17, 326–327 (1994).
    Google Scholar
  15. Grepin, C. et al. A hormone-encoding gene identifies a pathway for cardiac but not skeletal muscle gene transcription. Mol. Cell. Biol. 14, 3115–3129 (1994).
    Article CAS PubMed PubMed Central Google Scholar
  16. Ng, Y.K., George, K.M., Engel, J.D. & Linzer, D.I. GATA factor activity is required for the trophoblast-specific transcriptional regulation of the mouse placental lactogen I gene. Development 120, 3257–3266 (1994).
    CAS PubMed Google Scholar

Download references

Author information

Authors and Affiliations

  1. Departments of Molecular Biology and Oncology, The University of Texas Southwestern Medical Center at Dallas, 6000 Harry Mines Blvd., Dallas, Texas, 75235-9148, USA
    Anthony B. Firulli, David G. McFadden, Qing Lin, Deepak Srivastava & Eric N. Olson
  2. Pediatrics, The University of Texas Southwestern Medical Center at Dallas, 6000 Harry Mines Blvd., Dallas, Texas, 75235-9148, USA
    Deepak Srivastava

Authors

  1. Anthony B. Firulli
    You can also search for this author inPubMed Google Scholar
  2. David G. McFadden
    You can also search for this author inPubMed Google Scholar
  3. Qing Lin
    You can also search for this author inPubMed Google Scholar
  4. Deepak Srivastava
    You can also search for this author inPubMed Google Scholar
  5. Eric N. Olson
    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toEric N. Olson.

Rights and permissions

About this article

Cite this article

Firulli, A., McFadden, D., Lin, Q. et al. Heart and extra-embryonic mesodermal defects in mouse embryos lacking the bHLH transcription factor Hand1.Nat Genet 18, 266–270 (1998). https://doi.org/10.1038/ng0398-266

Download citation