Hes1 is expressed in the second heart field and is required for outflow tract development.
BACKGROUND
Rapid growth of the embryonic heart occurs by addition of progenitor cells of the second heart field to the poles of the elongating heart tube. Failure or perturbation of this process leads to congenital heart defects. In order to provide further insight into second heart field development we characterized the insertion site of a transgene expressed in the second heart field and outflow tract as the result of an integration site position effect.


RESULTS
Here we show that the integration site of the A17-Myf5-nlacZ-T55 transgene lies upstream of Hes1, encoding a basic helix-loop-helix containing transcriptional repressor required for the maintenance of diverse progenitor cell populations during embryonic development. Transgene expression in a subset of Hes1 expression sites, including the CNS, pharyngeal epithelia, pericardium, limb bud and lung endoderm suggests that Hes1 is the endogenous target of regulatory elements trapped by the transgene. Hes1 is expressed in pharyngeal endoderm and mesoderm including the second heart field. Analysis of Hes1 mutant hearts at embryonic day 15.5 reveals outflow tract alignment defects including ventricular septal defects and overriding aorta. At earlier developmental stages, Hes1 mutant embryos display defects in second heart field proliferation, a reduction in cardiac neural crest cells and failure to completely extend the outflow tract.


CONCLUSIONS
Hes1 is expressed in cardiac progenitor cells in the early embryo and is required for development of the arterial pole of the heart.
Rochais
Francesca
F
Developmental Biology Institute of Marseilles-Luminy, UMR 6216 CNRS-Université de la Méditerranée, Campus de Luminy, Marseille, France.
Dandonneau
Mathieu
M
Mesbah
Karim
K
Jarry
Thérèse
T
Mattei
Marie-Geneviève
MG
Kelly
Robert G
RG
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D015153:Blotting, Western; D049109:Cell Proliferation; D017931:DNA Primers; D006321:Heart / Q000196:embryology*; D018398:Homeodomain Proteins / Q000235:genetics*; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D009206:Myocardium / Q000378:metabolism*; D000072056:Transcription Factor HES-1; D019076:Transgenes
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D018398:Homeodomain Proteins; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse