Cardiac neural crest in zebrafish embryos contributes to myocardial cell lineage and early heart function

Abstract

Myocardial dysfunction is evident within hours after ablation of the cardiac neural crest in chick embryos, suggesting a role for neural crest in myocardial maturation that is separate from its role in outflow septation. This role could be conserved in an animal that does not have a divided systemic and pulmonary circulation, such as zebrafish. To test this hypothesis, we used cell marking to identify the axial level of neural crest that migrates to the heart in zebrafish embryos. Unlike the chick and mouse, the zebrafish cardiac neural crest does not originate from the axial level of the somites. The region of neural crest cranial to somite 1 was found to contribute cells to the heart. Cells from the cardiac neural crest migrated to the myocardial wall of the heart tube, where some of them expressed a myocardial phenotype. Laser ablation of the cardiac premigratory neural crest at the three-to four-somite stage resulted in loss of the neural crest cells migrating to the heart as shown by the absence of AP2-and HNK1-expressing cells and failure of the heart tube to undergo looping. Myocardial function was assessed 24 hr after the cardiac neural crest ablation in a subpopulation of embryos with normal heart rate. Decreased stroke volume, ejection fraction, and cardiac output were observed, indicating a more severe functional deficit in cardiac neural crest-ablated zebrafish embryos compared with neural crest-ablated chick embryos. These results suggest a new role for cardiac neural crest cells in vertebrate cardiac development and are the first report of a myocardial cell lineage for neural crest derivatives. Developmental Dynamics 226:540 -550, 2003.

Temporal–spatial ablation of neural crest in the mouse results in cardiovascular defects

“…Myocardial dysfunction in the chick after NCA has been found to be secondary to depressed L-type calcium current, excitation contraction coupling, and calcium sensitivity of the contractile apparatus (Creazzo et al, 1998). A similar myocardial dysfunction has been documented in NCA zebrafish (Li et al, 2003) and in the Pax3 mutant Splotch mouse (Conway et al, 1997a). Splotch mice have many phenotypic features that resemble the chick model of NCA and also die in utero mid-gestation around day 14 secondary to heart failure (Conway et al, 1997b).…”

Insulin-like growth factor-2 regulates early neural and cardiovascular system development in zebrafish embryos

“…This may be due to the defects in neural development in these embryos. The process of migration of cardiac neural crest cells to the heart has been conserved through evolution and, in zebrafish, cardiac neural crest cells migrate to the outflow tract and take on a myocardial cell lineage (Li et al, 2003). Therefore, we postulate that cardiac neural crest cell migration to both the outflow tract and myocardium may be disrupted in IGF-2a morphants and this may contribute to the cardiovascular defects observed in these embryos.…”

Requirement for Foxd3 in the maintenance of neural crest progenitors

“…For example, in the mother superior mutation, which is a mutation somewhere outside the coding region that affects only NC expression of foxd3, melanophores are delayed in their development but then recover, whereas iridophores remain greatly reduced (Montero-Balaguer et al, 2006). Zebrafish cardiac NC contributes primarily to the myocardial cell lineage (Li et al, 2003). Despite this, only one group reported a slight edema in the heart in foxd3 mutants (Montero-Balaguer et al, 2006).…”