Calreticulin is a secreted BMP antagonist, expressed in Hensen's node during neural induction

- A functional screen uncovers new secreted factors expressed by chick Hensen's node
- A yeast Signal Sequence Trap identifies candidates including Calreticulin and Calnexin.
- We show thatCalreticulin is secretedand binds to BMP4.
- Calreticulin acts as a BMP antagonist in vivo and in vitro.
- Calreticulin does not account for all organizer functions but may contribute to its complexity.

Hensen's node is the “organizer” of the avian and mammalian early embryo. It has many functions, including neural induction and patterning of the ectoderm and mesoderm. Some of the signals responsible for these activities are known but these do not explain the full complexity of organizer activity. Here we undertake a functional screen to discover new secreted factors expressed by the node at this time of development. Using a Signal Sequence Trap in yeast, we identify several candidates. Here we focus on Calreticulin. We show that in addition to its known functions in intracellular Calcium regulation and protein folding, Calreticulin is secreted, it can bind to BMP4 and act as a BMP antagonist in vivo and in vitro. Calreticulin is not sufficient to account for all organizer functions but may contribute to the complexity of its activity.