Author
Listed:
- Caitlin Ford
(Columbia University
Columbia University
Columbia University)
- Carmen Sena-Tomás
(Columbia University
Columbia University
Institut d’Investigacions Biomèdiques August Pi i Sunyer
University of Barcelona)
- Tint Tha Ra Wun
(Columbia University
Columbia University)
- Angelika G. Aleman
(Columbia University
Columbia University
Columbia University
Memorial Sloan Kettering Cancer Center)
- Uday Rangaswamy
(Scuola Internazionale Superiore di Studi Avanzati (SISSA))
- Jake Leyhr
(Uppsala University)
- María I. Nuñez
(Columbia University
Columbia University)
- Cynthia Zehui Gao
(Columbia University
Columbia University
Columbia University)
- Hieu T. Nim
(Murdoch Children’s Research Institute
The University of Melbourne
Monash University
Murdoch Children’s Research Institute)
- Michael See
(Murdoch Children’s Research Institute
Murdoch Children’s Research Institute)
- Ugo Coppola
(Cincinnati Children’s Hospital Medical Center
Florida Gulf Coast University)
- Joshua S. Waxman
(Cincinnati Children’s Hospital Medical Center
University of Cincinnati College of Medicine)
- Mirana Ramialison
(Murdoch Children’s Research Institute
The University of Melbourne
Monash University
Murdoch Children’s Research Institute)
- Tatjana Haitina
(Uppsala University)
- Joanna Smeeton
(Columbia University
Columbia University
Columbia University)
- Remo Sanges
(Scuola Internazionale Superiore di Studi Avanzati (SISSA)
Istituto Italiano di Tecnologia (IIT))
- Kimara L. Targoff
(Columbia University
Columbia University)
Abstract
Craniofacial malformations arise from developmental defects in the head, face, and neck with phenotypes such as 22q11.2 deletion syndrome illustrating a developmental link between cardiovascular and craniofacial morphogenesis. NKX2-5 is a key cardiac transcription factor associated with congenital heart disease and mouse models of Nkx2-5 deficiency highlight roles in cardiac development. In zebrafish, nkx2.5 and nkx2.7 are paralogues in the NK4 family expressed in cardiomyocytes and pharyngeal arches. Despite shared cellular origins of cardiac and craniofacial tissues, the function of NK4 factors in head and neck patterning has not been elucidated. Molecular evolutionary analysis of NK4 genes shows that nkx2.5 and nkx2.7 are ohnologs resulting from whole genome duplication events. Nkx2.7 serves as a previously unappreciated regulator of branchiomeric muscle and cartilage formation for which nkx2.5 cannot fully compensate. Mechanistically, our results highlight that Nkx2.7 patterns the cranial neural crest and functions upstream of Endothelin1 to inhibit Notch signals. Together, our studies shed light on an evolutionarily conserved Nkx transcription factor with unique functions in vertebrate craniofacial development, advancing our understanding of congenital head and neck deformities.
Suggested Citation
Caitlin Ford & Carmen Sena-Tomás & Tint Tha Ra Wun & Angelika G. Aleman & Uday Rangaswamy & Jake Leyhr & María I. Nuñez & Cynthia Zehui Gao & Hieu T. Nim & Michael See & Ugo Coppola & Joshua S. Waxman, 2025.
"Nkx2.7 is a conserved regulator of craniofacial development,"
Nature Communications, Nature, vol. 16(1), pages 1-19, December.
Handle:
RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58821-3
DOI: 10.1038/s41467-025-58821-3
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