Induction of initial cardiomyocyte alpha-actin--smooth muscle alpha-actin--in cultured avian pregastrula epiblast: a role for nodal and BMP antagonist.
During early cardiogenesis, endoderm-derived bone morphogenetic protein (BMP) induces the expression of both heart-specific transcription factors and sarcomeric proteins. However, BMP antagonists do not inhibit the expression of the "initial heart alpha-actin"--smooth muscle alpha-actin (SMA)--which is first expressed in the anterior lateral mesoderm and then recruited into the initial myofibrils (Nakajima et al. [2002] Dev. Biol. 245:291-303). Therefore, mechanisms that regulate the expression of SMA in the heart-forming mesoderm are not well-understood. Regional explantation experiments using chick blastoderm showed that the posterolateral region of the epiblast differentiated into cardiomyocytes. Posterior epiblast cultured with or without the associated hypoblast showed that interaction between the tissues of these two germ layers at the early pregastrula stage (stages X-XI) was a prerequisite for the expression of SMA. Posterior epiblast that is cultured without hypoblast could also be induced to express SMA if TGF-beta or activin was added to the culture medium. However, neither neutralizing antibodies against TGF-betas nor follistatin perturbed the expression of SMA in cultured blastoderm. Adding BMP to the cultured blastoderm inhibited the expression of SMA, whereas BMP antagonists, such as chordin, were able to induce the expression of SMA in cultured posterior epiblast. Furthermore, adding lefty-1, a nodal antagonist, to the blastoderm inhibited the expression of SMA, and nodal plus BMP antagonist up-regulated the expression of SMA in cultured posterior epiblast. Results indicate that the interaction between the tissues of the posterior epiblast and hypoblast is necessary to initiate the expression of SMA during early cardiogenesis and that nodal and BMP antagonist may play an important role in the regulation of SMA expression.
Department of Anatomy, Graduate School of Medicine, Osaka City University, Abenoku, Osaka, Japan.
Hiroko
H
Matsui
Kazuo
K
Ikeda
Kazuki
K
Nakatani
Masahide
M
Sakabe
Toshiyuki
T
Yamagishi
Toshio
T
Nakanishi
Yuji
Y
Nakajima
D000199:Actins / Q000378:metabolism*; D028341:Activins / Q000502:physiology; D000818:Animals; D001756:Blastoderm / Q000502:physiology; D036703:Blastula / Q000502:physiology*; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology; D002642:Chick Embryo; D004627:Embryonic Induction / Q000502:physiology; D038681:Follistatin / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D055458:Left-Right Determination Factors; D009130:Muscle, Smooth / Q000196:embryology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D055457:Nodal Protein; D016212:Transforming Growth Factor beta / Q000502:physiology*; D000099176:Noggin Protein
D000199:Actins; D028341:Activins; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D038681:Follistatin; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D055458:Left-Right Determination Factors; D055457:Nodal Protein; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; C054234:chordin