RT Journal Article
SR Electronic
T1 Apcdd1 is a dual BMP/Wnt inhibitor in the developing nervous system and skin
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 843714
DO 10.1101/843714
A1 Alin Vonica
A1 Neha Bhat
A1 Keith Phan
A1 Jinbai Guo
A1 Lăcrimioara Iancu
A1 Jessica A. Weber
A1 Amir Karger
A1 John W. Cain
A1 Etienne C. E. Wang
A1 Gina M. DeStefano
A1 Anne H. O’Donnell-Luria
A1 Angela M. Christiano
A1 Bruce Riley
A1 Samantha J. Butler
A1 Victor Luria
YR 2019
UL http://biorxiv.org/content/early/2019/11/15/843714.abstract
AB Animal development and homeostasis depend on precise temporal and spatial intercellular signaling. Components shared between signaling pathways, generally thought to decrease specificity, paradoxically can also provide a solution to pathway coordination. Here we show that the Bone Morphogenetic Protein (BMP) and Wnt signaling pathways share Apcdd1 as a common inhibitor and that Apcdd1 is a taxon-restricted gene with novel domains and signaling functions. Previously, we showed that Apcdd1 inhibits Wnt signaling, here we find that Apcdd1 potently inhibits BMP signaling in body axis formation and neural differentiation in chicken, frog, zebrafish, and humans. Our results from experiments and modeling suggest that Apcdd1 may coordinate the outputs of two signaling pathways central to animal development and human disease.Significance Statement Apcdd1 is a taxon-restricted gene that inhibits both BMP and Wnt intercellular signaling pathways in multiple organisms including mice, frog, zebrafish, and chicken. It encodes a bi-functional protein with a novel protein domain that can bind to Wnt and BMP receptors and block downstream signaling.