Blocking hedgehog signaling after ablation of the dorsal neural tube allows regeneration of the cardiac neural crest and rescue of outflow tract septation.


Journal Article

Cardiac neural crest cells (CNCC) migrate into the caudal pharynx and arterial pole of the heart to form the outflow septum. Ablation of the CNCC results in arterial pole malalignment and failure of outflow septation, resulting in a common trunk overriding the right ventricle. Unlike preotic cranial crest, the postotic CNCC do not normally regenerate. We applied the hedgehog signaling inhibitor, cyclopamine (Cyc), to chick embryos after CNCC ablation and found normal heart development at day 9 suggesting that the CNCC population was reconstituted. We ablated the CNCC, and labeled the remaining neural tube with DiI/CSRE and applied cyclopamine. Cells migrated from the neural tube in the CNCC-ablated, cyclopamine-treated embryos but not in untreated CNCC-ablated embryos. The newly generated cells followed the CNCC migration pathways, expressed neural crest markers and supported normal heart development. Finally, we tested whether reducing hedgehog signaling caused redeployment of the dorsal-ventral axis of the injured neural tube, allowing generation of new neural crest-like cells. The dorsal neural tube marker, Pax7, was maintained 12 h after CNCC ablation with Cyc treatment but not in the CNCC-ablated alone. This disruption of dorsal-ventral neural patterning permits a new wave of migratory cardiac neural crest-like cells.

Full Text

Cited Authors

  • Hutson, MR; Sackey, FN; Lunney, K; Kirby, ML

Published Date

  • November 2009

Published In

Volume / Issue

  • 335 / 2

Start / End Page

  • 367 - 373

PubMed ID

  • 19765571

Pubmed Central ID

  • 19765571

Electronic International Standard Serial Number (EISSN)

  • 1095-564X

International Standard Serial Number (ISSN)

  • 0012-1606

Digital Object Identifier (DOI)

  • 10.1016/j.ydbio.2009.09.013


  • eng