Wnt5a is required for cardiac outflow tract septation in mice

J. Robert Schleiffarth, Anthony D. Person, Brad J. Martinsen, David J. Sukovich, Ann Neumann, Clare V H Baker, Jamie L. Lohr, David N. Cornfield, Stephen C Ekker, Anna Petryk

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Lack of septation of the cardiac outflow tract (OFT) results in persistent truncus arteriosus (PTA), a form of congenital heart disease. The outflow myocardium expands through addition of cells originating from the pharyngeal mesoderm referred to as secondary/anterior heart field, whereas cardiac neural crest (CNC) cell-derived mesenchyme condenses to form an aortopulmonary septum. We show for the first time that a mutation in Wnt5a in mice leads to PTA. We provide evidence that Wnt5a is expressed in the pharyngeal mesoderm adjacent to CNC cells in both mouse and chicken embryos and in the myocardial cell layer of the conotruncus at the time when CNC cells begin to form the aortopulmonary septum in mice. Although expression domains of secondary heart field markers are not altered in Wnt5a mutant embryos, the expression of CNC cell marker PlexinA2 is significantly reduced. Stimulation of CNC cells with Wnt5a protein elicits Ca2+ transients, suggesting that CNC cells are capable of responding to Wnt5a. We propose a novel model in which Wnt5a produced in the OFT by cells originating from the pharyngeal mesoderm signals to adjacent CNC cells during formation of the aortopulmonary septum through a noncanonical pathway via localized intracellular increases in Ca2+.

Original languageEnglish (US)
Pages (from-to)386-391
Number of pages6
JournalPediatric Research
Volume61
Issue number4
DOIs
StatePublished - Apr 2007
Externally publishedYes

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Neural Crest
Mesoderm
Persistent Truncus Arteriosus
Embryonic Structures
Chickens
Heart Diseases
Myocardium
Mutation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Schleiffarth, J. R., Person, A. D., Martinsen, B. J., Sukovich, D. J., Neumann, A., Baker, C. V. H., ... Petryk, A. (2007). Wnt5a is required for cardiac outflow tract septation in mice. Pediatric Research, 61(4), 386-391. https://doi.org/10.1203/pdr.0b013e3180323810

Wnt5a is required for cardiac outflow tract septation in mice. / Schleiffarth, J. Robert; Person, Anthony D.; Martinsen, Brad J.; Sukovich, David J.; Neumann, Ann; Baker, Clare V H; Lohr, Jamie L.; Cornfield, David N.; Ekker, Stephen C; Petryk, Anna.

In: Pediatric Research, Vol. 61, No. 4, 04.2007, p. 386-391.

Research output: Contribution to journalArticle

Schleiffarth, JR, Person, AD, Martinsen, BJ, Sukovich, DJ, Neumann, A, Baker, CVH, Lohr, JL, Cornfield, DN, Ekker, SC & Petryk, A 2007, 'Wnt5a is required for cardiac outflow tract septation in mice', Pediatric Research, vol. 61, no. 4, pp. 386-391. https://doi.org/10.1203/pdr.0b013e3180323810
Schleiffarth JR, Person AD, Martinsen BJ, Sukovich DJ, Neumann A, Baker CVH et al. Wnt5a is required for cardiac outflow tract septation in mice. Pediatric Research. 2007 Apr;61(4):386-391. https://doi.org/10.1203/pdr.0b013e3180323810
Schleiffarth, J. Robert ; Person, Anthony D. ; Martinsen, Brad J. ; Sukovich, David J. ; Neumann, Ann ; Baker, Clare V H ; Lohr, Jamie L. ; Cornfield, David N. ; Ekker, Stephen C ; Petryk, Anna. / Wnt5a is required for cardiac outflow tract septation in mice. In: Pediatric Research. 2007 ; Vol. 61, No. 4. pp. 386-391.
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