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SPC4/PACE4 regulates a TGFβ signaling network during axis formation
Open accessAbstract
In vertebrates, specification of anteroposterior (A/P) and left–right (L/R) axes depends on TGFβ-related signals, including Nodal, Lefty, and BMPs. Endoproteolytic maturation of these proteins is probably mediated by the proprotein convertase SPC1/Furin. In addition, precursor processing may be regulated by related activities such as SPC4 (also known as PACE4). Here, we show that a proportion of embryos lacking SPC4 develop situs ambiguus combined with left pulmonary isomerism or complex craniofacial malformations including cyclopia, or both. Gene expression analysis during early somite stages indicates that spc4 is genetically upstream of nodal, pitx2, lefty1, and lefty2 and perhaps maintains the balance between Nodal and BMP signaling in the lateral plate that is critical for L/R axis formation. Furthermore, genetic interactions between nodal and spc4, together with our analysis of chimeric embryos, strongly suggest that during A/P axis formation, SPC4 acts primarily in the foregut. These findings establish an important role for SPC4 in patterning the early mouse embryo.
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Citations
Cited by
The biology and therapeutic targeting of the proprotein convertases
Seidah, N. G., & Prat, A. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3699 · Cited by 759
Establishment of vertebrate left–right asymmetry
Hamada, H., Meno, C., Watanabe, D., & Saijoh, Y. (2002) · Nature Reviews Genetics · doi:10.1038/nrg732 · Cited by 489
The activation and physiological functions of the proprotein convertases
Seidah, N. G., Mayer, G., Zaid, A., Rousselet, E., Nassoury, N., Poirier, S., Essalmani, R., & Prat, A. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2008.01.030 · Cited by 314
Arnold, S. J., Hofmann, U. K., Bikoff, E. K., & Robertson, E. J. (2008) · Development · doi:10.1242/dev.014357 · Cited by 271
Self-citationIn vivo evidence that furin from hepatocytes inactivates PCSK9
Essalmani, R., Susan-Resiga, D., Chamberland, A., Abifadel, M., Creemers, J. W., Boileau, C., Seidah, N. G., & Prat, A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.192104 · Cited by 144
Metadata
- Authors
- Constam, D. B., & Robertson, E. J.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2000-05-01
- Volume
- 14
- Issue
- 9
- Pages
- 1146-1155
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2099023864
- Cited by
- 185
- References
- 0
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Constam, D. B., & Robertson, E. J. (2000). SPC4/PACE4 regulates a TGFβ signaling network during axis formation. Genes & Development. https://doi.org/10.1101/gad.14.9.1146
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