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
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
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).
Srivastava, D., Cserjesi, P. & Olson, E.N. A subclass of bHLH proteins required for cardiac morphogenesis. Science 270, 1995–1999 (1995).
Cross, J.C. et al. Hxt encodes a basic helix-loop-helix transcription factor that regulates trophoblast cell development. Development 121, 2513–2523 (1995).
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).
Srivastava, D. et al. Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND. Nature Genet. 16, 154–160 (1997).
Olson, E.N. & Srivastava, D. Molecular pathways controlling heart development. Science 272, 671–676 (1996).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Author information
Authors and Affiliations
Corresponding author
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ng0398-266
This article is cited by
-
HAND factors regulate cardiac lineage commitment and differentiation from human pluripotent stem cells
Stem Cell Research & Therapy (2024)
-
RGS2 promotes estradiol biosynthesis by trophoblasts during human pregnancy
Experimental & Molecular Medicine (2023)
-
Induced Pluripotent Stem Cell–Based Modeling of Single-Ventricle Congenital Heart Diseases
Current Cardiology Reports (2023)
-
Formation of the Heart: Defining Cardiomyocyte Progenitors at Single-Cell Resolution
Current Cardiology Reports (2023)
-
Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma
Nature Communications (2022)