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XB-ART-50236
Dev Cell. March 23, 2015; 32 (6): 719-30.

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

Zhang X , Cheong SM , Amado NG , Reis AH , MacDonald BT , Zebisch M , Jones EY , Abreu JG , He X .


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.

PubMed ID: 25771893
PMC ID: PMC4375027
Article link: Dev Cell.
Grant support: R01 GM057603 NIGMS NIH HHS , P30 HD018655 NICHD NIH HHS , 090532/Z/09/Z Wellcome Trust , 090532/Z/09/Z Wellcome Trust , P30 HD-18655 NICHD NIH HHS , R01-GM057603 NIGMS NIH HHS , R01 GM057603 NIGMS NIH HHS , P30 HD018655 NICHD NIH HHS , A10976 Cancer Research UK, 090532/Z/09/Z Wellcome Trust , P30 HD-18655 NICHD NIH HHS , R01-GM057603 NIGMS NIH HHS , R01 GM057603 NIGMS NIH HHS , P30 HD018655 NICHD NIH HHS , A10976 Cancer Research UK

Genes referenced: actl6a ag1 bmp4 chrd.1 dkk1 dvl2 eef1a1 egr2 fgf2 foxg1 gnpda1 gpc3 gpc4 gsc hoxb9 lrp6 msx1 nodal1 nodal3.1 nog not notum odc1 otx2 pax6 sox2 t tbx2 trabd2a trabd2b tubb2b ventx2.2 wnt3a wnt5a wnt8a xk81a1

Antibodies referenced: Dvl2 Ab3 Lrp6 Ab1 Notum Ab1 Wnt3a Ab1 Wnt5a Ab2
Morpholinos referenced: Notum MO1 Notum MO2

References:
Alexandre, 2014, Pubmed[+]


Article Images: [+] show captions

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