Articles |
From the Department of Obstetrics and Gynecology (D.A.R., Y.P.), the Department of Cell and Molecular Biology and Feinberg Cardiovascular Research Institute (D.A.R.), and the Department of Pathology (A.I.), Northwestern University Medical School, Chicago, Ill, and the Center for Reproductive Sciences (D.A.R.), Northwestern University, Evanston, Ill.
Correspondence to Daniel A. Rappolee, PhD, Department of Obstetrics and Gynecology, Northwestern University Medical School, 303 E Chicago Ave, Tarry Building 4-725, Chicago, IL 60611. E-mail drappo@casbah.acns.nwu.edu.
Abstract In the mouse, the heart primordium arises when
mesoderm is set aside during gastrulation, is induced by pharyngeal
endoderm, migrates ventrally to the midline of the embryo, forms a
tube, and begins beating. Little is known of the molecular mechanisms
that mediate the determination, mitosis, differentiation, and migration
that lead to the beating heart. Transcripts for hepatocyte
growth factor/scatter factor (HGF) and its receptor are coexpressed
transiently and dynamically in the premyocardium but
not in other heart progenitor cells. Transcripts for HGF ligand and
receptor are first detected before cardiac function and looping and
persist through the first looping stage, when heart morphology begins
to elaborate. HGF ligand and receptor mRNA are detectable after the
putative heart transcription factor, Csx/Nkx2-5, and concomitantly with
the heart structural gene, cardiac actin. HGF receptor mRNA is detected
in the mesoderm of the headfold stage and persists in myocardial
precursors of the ventricles and atria (but not in the
outflow-tract smooth muscle cells) through the 14-somite stage at
8.75 days after fertilization (day E8.75). At the headfold stage,
between E7.5 and E8.0, HGF receptor mRNA was detected in myocardial
cells before fusion at the ventral midline. HGF ligand and receptor
mRNA transcripts are coexpressed in the embryo, except in the headfold
stage (when only the HGF receptor can be detected) and in the heart at
the 14- to 18-somite stage (when only HGF ligand can be detected). The
dynamic pattern of coexpression suggests an autoregulatory role for HGF
and its receptor in early heart development.
Key Words: hepatocyte growth factor/scatter factor hepatocyte growth factor receptor/c-met proto-oncogene cardiogenesis myocardium in situ hybridization
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