Return to search results Title: Bighead is a Wnt antagonist secreted by the Xenopus Spemann organizer that promotes Lrp6 endocytosis

Summary

The Xenopus laevis embryo has been subjected to almost saturating screens for molecules specifically expressed in dorsal Spemann organizer tissue. In this study, we performed high-throughput RNA sequencing of ectodermal explants, called animal caps, which normally give rise to epidermis. We analyzed dissociated animal cap cells that, through sustained activation of MAPK, differentiate into neural tissue. We also microinjected mRNAs for Cerberus, Chordin, FGF8, BMP4, Wnt8, and Xnr2, which induce neural or other germ layer differentiations. The searchable database provided here represents a valuable resource for the early vertebrate cell differentiation. These analyses resulted in the identification of a gene present in frog and fish, which we call Bighead. Surprisingly, at gastrula, it was expressed in the Spemann organizer and endoderm, rather than in ectoderm as we expected. Despite the plethora of genes already mined from Spemann organizer tissue, Bighead encodes a secreted protein that proved to be a potent inhibitor of Wnt signaling in a number of embryological and cultured cell signaling assays. Overexpression of Bighead resulted in large head structures very similar to those of the well-known Wnt antagonists Dkk1 and Frzb-1. Knockdown of Bighead with specific antisense morpholinos resulted in embryos with reduced head structures, due to increased Wnt signaling. Bighead protein bound specifically to the Wnt coreceptor lipoprotein receptor-related protein 6 (Lrp6), leading to its removal from the cell surface. Bighead joins two other Wnt antagonists, Dkk1 and Angptl4, which function as Lrp6 endocytosis regulators. These results suggest that endocytosis plays a crucial role in Wnt signaling.

Contributors: Edward De Robertis, Yi Ding, Gabriele Colozza, Eric Sosa, Yuki Moriyama, Samantha Rundle, Lukasz Salwinski

Experiment Type: A genome-wide study of the effects of vavious growth factors and dissociation on animal caps of Xenopus laevis

Experiment Reagents: bmp4, cer1, chrd, [-][+]


Article: XB-ART-55302, PubMed

Source: NCBI GEO, Xenbase Download

Sample	View		GSMs	Assay Type
animal cap explant - NF12 GSM2835917  GSM2835921  GSM2835923  GSM2835927  RNA-Seq Xla   [-] [+] Background: Xla.pigmentedNasco Manipulations: Manipulation Type Reagent Target Gene Stage Treatment Area explant   NF stage 9 animal cap Conditions: Tissue Assay Stages ChIP Antibody animal cap NF stage 12      animal cap explant + bmp4 - NF12 DEG GSM2835919  RNA-Seq Xla   [-] [+] Background: Xla.Outbred Manipulations: Manipulation Type Reagent Target Gene Stage Treatment Area mRNA injection bmp4 (Xla) bmp4 (Xla) NF stage 2 (2-cell) blastomere explant   NF stage 9 animal cap Conditions: Tissue Assay Stages ChIP Antibody animal cap NF stage 12      animal cap explant + cer1 - NF12 DEG GSM2835926  RNA-Seq Xla   [-] [+] Background: Xla.Outbred Manipulations: Manipulation Type Reagent Target Gene Stage Treatment Area mRNA injection cer1 (Xla) cer1 (Xla) NF stage 2 (2-cell) blastomere explant   NF stage 9 animal cap Conditions: Tissue Assay Stages ChIP Antibody animal cap NF stage 12      animal cap explant + chrd.1 - NF12 DEG GSM2835920  RNA-Seq Xla   [-] [+] Background: Xla.Outbred Manipulations: Manipulation Type Reagent Target Gene Stage Treatment Area mRNA injection chrd (Xla) chrd (Xla) NF stage 2 (2-cell) blastomere explant   NF stage 9 animal cap Conditions: Tissue Assay Stages ChIP Antibody animal cap NF stage 12      animal cap explant+ fgf8 - NF12 DEG GSM2835928  RNA-Seq Xla   [-] [+] Background: Xla.Outbred Manipulations: Manipulation Type Reagent Target Gene Stage Treatment Area mRNA injection fgf8 (Xla) fgf8 (Xla) NF stage 2 (2-cell) blastomere explant   NF stage 9 animal cap Conditions: Tissue Assay Stages ChIP Antibody animal cap NF stage 12      animal cap explant + nodal2 - NF12 DEG GSM2835929  RNA-Seq Xla   [-] [+] Background: Xla.Outbred Manipulations: Manipulation Type Reagent Target Gene Stage Treatment Area mRNA injection nodal2 (Xla) nodal2 (Xla) NF stage 2 (2-cell) blastomere explant   NF stage 9 animal cap Conditions: Tissue Assay Stages ChIP Antibody animal cap NF stage 12      animal cap explant + tissue dissociation - NF12 DEG GSM2835918  GSM2835922  GSM2835924  RNA-Seq Xla   [-] [+] Background: Xla.pigmentedNasco Manipulations: Manipulation Type Reagent Target Gene Stage Treatment Area explant   NF stage 9 animal cap environmental treatment tissue dissociation NF stage 9 animal cap Conditions: Tissue Assay Stages ChIP Antibody animal cap NF stage 12      animal cap explant + wnt8a - NF12 DEG GSM2835925  RNA-Seq Xla   [-] [+] Background: Xla.Outbred Manipulations: Manipulation Type Reagent Target Gene Stage Treatment Area mRNA injection wnt8a (Xla) wnt8a (Xla) NF stage 2 (2-cell) blastomere explant   NF stage 9 animal cap Conditions: Tissue Assay Stages ChIP Antibody animal cap NF stage 12      animal cap explant + wnt8a + nodal2 - NF12 DEG GSM2835930  RNA-Seq Xla   [-] [+] Background: Xla.Outbred Manipulations: Manipulation Type Reagent Target Gene Stage Treatment Area mRNA injection wnt8a (Xla) wnt8a (Xla) NF stage 2 (2-cell) blastomere mRNA injection nodal2 (Xla) nodal2 (Xla) NF stage 2 (2-cell) blastomere explant   NF stage 9 animal cap Conditions: Tissue Assay Stages ChIP Antibody animal cap NF stage 12   dorsal embryo explant - NF12 GSM2835931  RNA-Seq Xla   [-] [+] Background: Xla.pigmentedNasco Manipulations: Manipulation Type Reagent Target Gene Stage Treatment Area explant   NF stage 10 dorsal Conditions: Tissue Assay Stages ChIP Antibody dorsal NF stage 12   ventral embryo explant - NF12 GSM2835932  RNA-Seq Xla   [-] [+] Background: Xla.pigmentedNasco Manipulations: Manipulation Type Reagent Target Gene Stage Treatment Area explant   NF stage 10 ventral Conditions: Tissue Assay Stages ChIP Antibody ventral NF stage 12

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