A caudal proliferating growth center contributes to both poles of the forming heart tube.
Recent studies have shown that the primary heart tube continues to grow by addition of cells from the coelomic wall. This growth occurs concomitantly with embryonic folding and formation of the coelomic cavity, making early heart formation morphologically complex. A scarcity of data on localized growth parameters further hampers the understanding of cardiac growth. Therefore, we investigated local proliferation during early heart formation. Firstly, we determined the cell cycle length of primary myocardium of the early heart tube to be 5.5 days, showing that this myocardium is nonproliferating and implying that initial heart formation occurs solely by addition of cells. In line with this, we show that the heart tube rapidly lengthens at its inflow by differentiation of recently divided precursor cells. To track the origin of these cells, we made quantitative 3D reconstructions of proliferation in the forming heart tube and the mesoderm of its flanking coelomic walls. These reconstructions show a single, albeit bilateral, center of rapid proliferation in the caudomedial pericardial back wall. This center expresses Islet1. Cell tracing showed that cells from this caudal growth center, besides feeding into the venous pole of the heart, also move cranially via the dorsal pericardial mesoderm and differentiate into myocardium at the arterial pole. Inhibition of caudal proliferation impairs the formation of both the atria and the right ventricle. These data show how a proliferating growth center in the caudal coelomic wall elongates the heart tube at both its venous and arterial pole, providing a morphological mechanism for early heart formation.
van den Berg
Gert
G
Heart Failure Research Center, Academic Medical Center, Amsterdam, The Netherlands.
Abu-Issa
Radwan
R
de Boer
Bouke A
BA
Hutson
Mary R
MR
de Boer
Piet A J
PA
Soufan
Alexandre T
AT
Ruijter
Jan M
JM
Kirby
Margaret L
ML
van den Hoff
Maurice J B
MJ
Moorman
Antoon F M
AF
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002642:Chick Embryo; D006321:Heart / Q000196:embryology*; D006352:Heart Ventricles / Q000196:embryology; D018398:Homeodomain Proteins / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D060850:LIM-Homeodomain Proteins; D008648:Mesoderm / Q000166:cytology; D008953:Models, Anatomic; D008955:Models, Cardiovascular; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D038081:Organogenesis; D010496:Pericardium / Q000196:embryology; D013997:Time Factors; D014157:Transcription Factors
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D001973:Bromodeoxyuridine