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  4. The nodal precursor acting via activin receptors induces mesoderm by maintaining a source of its convertases and BMP4
 
research article

The nodal precursor acting via activin receptors induces mesoderm by maintaining a source of its convertases and BMP4

Ben-Haim, N.
•
Lu, C.
•
Guzman-Ayala, M.
Show more
2006
Developmental Cell

During early mouse development, the subtilisin-like proprotein convertases (SPC) Furin and PACE4 pattern the primitive ectoderm and visceral endoderm, presumably by activating the TGFss-related Nodal precursor. Here, mutation of the SPC motif provides direct evidence that Nodal processing is essential to specify anterior visceral endoderm and mesendoderm. Surprisingly, however, the Nodal precursor binds and activates activin receptors to maintain expression of Furin, PACE4, and Bmp4 in extraembryonic ectoderm at a distance from the Nodal source. In return, Bmp4 induces Wnt3, which amplifies Nodal expression in the epiblast and mediates induction of mesoderm. We conclude that uncleaved Nodal sustains the extraembryonic source of proprotein convertases and Bmp4 to amplify Nodal signaling in two nonredundant feedback loops with dual timescales and to localize primitive streak formation at the posterior pole. Based on mathematical modeling, we discuss how these sequential loops control cell fate.

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Type
research article
DOI
10.1016/j.devcel.2006.07.005
Web of Science ID

WOS:000240533800007

Author(s)
Ben-Haim, N.
Lu, C.
Guzman-Ayala, M.
Pescatore, L.
Mesnard, D.
Bischofberger, M.  
Naef, F.  
Robertson, E. J.
Constam, D. B.  
Date Issued

2006

Published in
Developmental Cell
Volume

11

Issue

3

Start page

313

End page

23

Note

Ecole Polytechnique Federale de Lausanne EPFL-ISREC, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland.

Editorial or Peer reviewed

REVIEWED

Written at

OTHER

EPFL units
UPCDA  
UPNAE  
Available on Infoscience
December 13, 2007
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/15623
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