Rotation and asymmetric development of the zebrafish heart requires directed migration of cardiac progenitor cells.
We have used high-resolution 4D imaging of cardiac progenitor cells (CPCs) in zebrafish to investigate the earliest left-right asymmetric movements during cardiac morphogenesis. Differential migratory behavior within the heart field was observed, resulting in a rotation of the heart tube. The leftward displacement and rotation of the tube requires hyaluronan synthase 2 expression within the CPCs. Furthermore, by reducing or ectopically activating BMP signaling or by implantation of BMP beads we could demonstrate that BMP signaling, which is asymmetrically activated in the lateral plate mesoderm and regulated by early left-right signals, is required to direct CPC migration and cardiac rotation. Together, these results support a model in which CPCs migrate toward a BMP source during development of the linear heart tube, providing a mechanism by which the left-right axis drives asymmetric development of the vertebrate heart.
Smith
Kelly A
KA
Hubrecht Institute for Developmental Biology and Stem Cell Research, 3584 CT Utrecht, The Netherlands.
Chocron
Sonja
S
von der Hardt
Sophia
S
de Pater
Emma
E
Soufan
Alexander
A
Bussmann
Jeroen
J
Schulte-Merker
Stefan
S
Hammerschmidt
Matthias
M
Bakkers
Jeroen
J
D000818:Animals; D019521:Body Patterning / Q000187:drug effects; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D019070:Cell Lineage / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000196:embryology*; D006801:Humans; D000076002:Hyaluronan Synthases; D055458:Left-Right Determination Factors; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects; D009154:Mutation / Q000235:genetics; D009206:Myocardium / Q000166:cytology*; D012399:Rotation; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; C526161:LEFTY1 protein, human; D055458:Left-Right Determination Factors; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases; C491095:has2 protein, zebrafish