This Article Full Text Full Text (PDF) All Versions of this Article: 92/1/73    most recent 01.RES.0000050587.76563.A5v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schäfer, K. Articles by Braun, T. Search for Related Content PubMed PubMed Citation Articles by Schäfer, K. Articles by Braun, T. Related Collections Other myocardial biology Gene expression Myogenesis

(Circulation Research. 2003;92:73.)
© 2003 American Heart Association, Inc.

Molecular Medicine

The Homeobox Gene Lbx1 Specifies a Subpopulation of Cardiac Neural Crest Necessary for Normal Heart Development

Konstanze Schäfer, Petra Neuhaus, Julia Kruse, Thomas Braun

From the Institute of Physiological Chemistry, University of Halle-Wittenberg, Halle, Germany.

Correspondence to Thomas Braun, MD, PhD, Institute of Physiological Chemistry, Hollystr. 1, Halle 06097, Germany. E-mail thomas.braun{at}medizin.uni-halle.de

Cardiac neural crest cells are known to play multiple roles during development of the inflow and outflow tract of the heart and the aortic arch. In addition, cardiac neural crest is required for normal heart tube looping and regulation of myocardial cell proliferation, as well as differentiation and function of the myocardium. We show that the homeobox gene Lbx1 is expressed in a subpopulation of the cardiac neural crest during tubular heart formation. Inactivation of the Lbx1 gene in mice resulted in defects in heart looping, changes in gene expression pattern, and increased cell proliferation ensuing in myocardial hyperplasia. We found that the activity of the Lbx1 promoter, as indicated by a LacZ reporter gene, is upregulated in the hearts of Lbx1^+/-:splotch^1H/splotch^1H and Lbx1^-/- mice, indicating that Pax3 and Lbx1 participate in a negative regulatory feedback that might be necessary for normal differentiation and function of the myocardium during early heart development. Because migration of Lbx1-expressing neural crest cells was not altered in Lbx1^-/- embryos, we postulate that Lbx1 gene function is critical for specification of a subpopulation of cardiac neural crest subsequent to migration.

Key Words: Lbx1 • cardiac neural crest • mouse mutants • hyperplasia • Pax3

This article has been cited by other articles:

				S. D. Kumar, S.-K. Yong, S. T. Dheen, B.-H. Bay, and S. S.-W. Tay Cardiac Malformations Are Associated with Altered Expression of Vascular Endothelial Growth Factor and Endothelial Nitric Oxide Synthase Genes in Embryos of Diabetic Mice Experimental Biology and Medicine, November 1, 2008; 233(11): 1421 - 1432. [Abstract] [Full Text] [PDF]

				X. Sun, R. Zhang, X. Lin, and X. Xu Wnt3a Regulates the Development of Cardiac Neural Crest Cells by Modulating Expression of Cysteine-Rich Intestinal Protein 2 in Rhombomere 6 Circ. Res., April 11, 2008; 102(7): 831 - 839. [Abstract] [Full Text] [PDF]

				M. Zmojdzian, J. P. Da Ponte, and K. Jagla Cellular components and signals required for the cardiac outflow tract assembly in Drosophila PNAS, February 19, 2008; 105(7): 2475 - 2480. [Abstract] [Full Text] [PDF]

				H. Ebelt, N. Hufnagel, P. Neuhaus, H. Neuhaus, P. Gajawada, A. Simm, U. Muller-Werdan, K. Werdan, and T. Braun Divergent Siblings: E2F2 and E2F4 but not E2F1 and E2F3 Induce DNA Synthesis in Cardiomyocytes Without Activation of Apoptosis Circ. Res., March 18, 2005; 96(5): 509 - 517. [Abstract] [Full Text] [PDF]

				M. Zikova, J.-P. Da Ponte, B. Dastugue, and K. Jagla Patterning of the cardiac outflow region in Drosophila PNAS, October 14, 2003; 100(21): 12189 - 12194. [Abstract] [Full Text] [PDF]