TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development.
C, D., OK, T., DA, B., Y, A., MVK, S., E, A., LJ, J., PM, T., JB, M., & MS, H. (2026). TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development.. PLoS biology. https://doi.org/10.1371/journal.pbio.3003902
C D, OK T, DA B, Y A, MVK S, E A, et al. TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development.. PLoS biology. 2026; doi: 10.1371/journal.pbio.3003902
C D, OK T, DA B, et al. TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development.[J]. PLoS biology. 2026. DOI: 10.1371/journal.pbio.3003902.
@article{c2026,
author = {Doganli C and Thomsen OK and Baird DA and Ali Y and Sarusie MVK and Audain E and Jessen LJ and Truelsen PM and Mogensen JB and Holm MS},
title = {TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development.},
journal = {PLoS biology},
year = {2026},
doi = {10.1371/journal.pbio.3003902},
note = {PMID: 42550797},
}
TY - JOUR AU - Doganli C AU - Thomsen OK AU - Baird DA AU - Ali Y AU - Sarusie MVK AU - Audain E AU - Jessen LJ AU - Truelsen PM AU - Mogensen JB AU - Holm MS TI - TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development. T2 - PLoS biology PY - 2026 DO - 10.1371/journal.pbio.3003902 AN - PMID:42550797 ER -
Pathogenic variants in the genes encoding the non-canonical TGFB signaling components TAK1 (MAP3K7), TAB2 and PKA-Cα (PRKACA) cause rare multisystem disorders, which may include congenital heart disease (CHD). To investigate the role of TAK1 signaling in CHD, we performed genetic analysis of CHD patients and discovered an increased burden of rare TAB2 and TAK1 variants in patients with extracardiac abnormalities. To address the mechanism of TAK1 in heart development, we performed experiments in cell and animal models. Zebrafish tak1 and tab2 mutants presented with cardiac and extracardiac developmental defects, and tak1 mutant hearts showed downregulation of genes encoding core cardiac transcription factors, sarcomeric proteins and extracellular matrix proteins. In vitro experiments indicated that TAK1 via TAB2 and PKA-Cα is activated at the primary cilium during cardiomyogenesis; activation at this site is enhanced by TGFB/BMP ligands. Inactivation of TAK1 inhibited ciliary signaling and cardiomyocyte differentiation, and patient-derived TAK1 variants reduced its ciliary localization. In conclusion, our data establish a pivotal role for TAK1 and its upstream regulators at the primary cilium in heart development and syndromic CHD.