title: Heart field origin of great vessel precursors relies on nkx2.5-mediated vasculogenesis.
abstract: The pharyngeal arch arteries (PAAs) are transient embryonic blood vessels that make indispensable contributions to the carotid arteries and great vessels of the heart, including the aorta and pulmonary arteries. During embryogenesis, the PAAs appear in a craniocaudal sequence to connect pre-existing segments of the primitive circulation after de novo vasculogenic assembly from angioblast precursors. Despite the unique spatiotemporal characteristics of PAA development, the embryonic origins of PAA angioblasts and the genetic factors regulating their emergence remain unknown. Here, we identify the embryonic source of PAA endothelium as nkx2.5(+) progenitors in lateral plate mesoderm long considered to adopt cell fates within the heart exclusively. Further, we report that PAA endothelial differentiation relies on Nkx2.5, a canonical cardiac transcription factor not previously implicated in blood vessel formation. Together, these studies reveal the heart field origin of PAA endothelium and attribute a new vasculogenic function to the cardiac transcription factor Nkx2.5 during great vessel precursor development.
authors.affiliation: 1] Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA [2] Harvard Medical School, Boston, Massachusetts 02115, USA [3] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA.
authors.forename: Noëlle
authors.initials: N
authors.lastname: Paffett-Lugassy
authors.forename: Reena
authors.initials: R
authors.lastname: Singh
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Nevis
authors.forename: Burcu
authors.initials: B
authors.lastname: Guner-Ataman
authors.forename: Evan
authors.initials: E
authors.lastname: O'Loughlin
authors.forename: Leila
authors.initials: L
authors.lastname: Jahangiri
authors.forename: Richard P
authors.initials: RP
authors.lastname: Harvey
authors.forename: C Geoffrey
authors.initials: CG
authors.lastname: Burns
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Burns
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D000072576:Homeobox Protein Nkx-2.5; D014157:Transcription Factors / Q000235:genetics*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D000072576:Homeobox Protein Nkx-2.5; C528182:Nkx2.5 protein, zebrafish; D014157:Transcription Factors; D029961:Zebrafish Proteins