Format

Send to

Choose Destination
Dev Cell. 2015 Mar 23;32(6):719-30. doi: 10.1016/j.devcel.2015.02.014. Epub 2015 Mar 12.

Notum is required for neural and head induction via Wnt deacylation, oxidation, and inactivation.

Author information

1
Department of Neurology, The F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
2
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
3
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
4
Department of Neurology, The F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: xi.he@childrens.harvard.edu.

Abstract

Secreted Wnt morphogens are essential for embryogenesis and homeostasis and require a lipid/palmitoleoylate modification for receptor binding and activity. Notum is a secreted Wnt antagonist that belongs to the α/β hydrolase superfamily, but its mechanism of action and roles in vertebrate embryogenesis are not fully understood. Here, we report that Notum hydrolyzes the Wnt palmitoleoylate adduct extracellularly, resulting in inactivated Wnt proteins that form oxidized oligomers incapable of receptor binding. Thus, Notum is a Wnt deacylase, and palmitoleoylation is obligatory for the Wnt structure that maintains its active monomeric conformation. Notum is expressed in naive ectoderm and neural plate in Xenopus and is required for neural and head induction. These findings suggest that Notum is a prerequisite for the "default" neural fate and that distinct mechanisms of Wnt inactivation by the Tiki protease in the Organizer and the Notum deacylase in presumptive neuroectoderm orchestrate vertebrate brain development.

PMID:
25771893
PMCID:
PMC4375027
DOI:
10.1016/j.devcel.2015.02.014
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center