PUBLICATION
Organizer restriction through modulation of Bozozok stability by the E3 ubiquitin ligase Lnx-like
- Authors
- Ro, H., and Dawid, I.B.
- ID
- ZDB-PUB-090814-11
- Date
- 2009
- Source
- Nature cell biology 11(9): 1121-1127 (Journal)
- Registered Authors
- Dawid, Igor B.
- Keywords
- none
- MeSH Terms
-
- Animals
- Body Patterning/drug effects
- Cell Line
- Goosecoid Protein/metabolism
- Homeodomain Proteins/metabolism*
- Humans
- Oligonucleotides, Antisense/pharmacology
- Organizers, Embryonic/drug effects
- Organizers, Embryonic/enzymology*
- Polyubiquitin/metabolism
- Protein Binding/drug effects
- Protein Stability/drug effects
- Ubiquitin-Protein Ligases/metabolism*
- Ubiquitination/drug effects
- Zebrafish/embryology*
- Zebrafish Proteins/deficiency
- Zebrafish Proteins/metabolism*
- PubMed
- 19668196 Full text @ Nat. Cell Biol.
Citation
Ro, H., and Dawid, I.B. (2009) Organizer restriction through modulation of Bozozok stability by the E3 ubiquitin ligase Lnx-like. Nature cell biology. 11(9):1121-1127.
Abstract
The organizer anchors the primary embryonic axis, and balance between dorsal (organizer) and ventral domains is fundamental to body patterning. LNX (ligand of Numb protein-X) is a RING finger and four PDZ domain-containing E3 ubiquitin ligase. LNX serves as a binding platform and may have a role in cell fate determination, but its in vivo functions are unknown. Here we show that Lnx-l (Lnx-like) functions as a critical regulator of dorso-ventral axis formation in zebrafish. Depletion of Lnx-l using specific antisense morpholinos (MOs) caused strong embryonic dorsalization. We identified Bozozok (Boz, also known as Dharma or Nieuwkoid) as a binding partner and substrate of Lnx-l. Boz is a homeodomain-containing transcriptional repressor induced by canonical Wnt signalling that is critical for dorsal organizer formation. Lnx-l induced K48-linked polyubiquitylation of Boz, leading to its proteasomal degradation in human 293T cells and in zebrafish embryos. Dorsalization induced by Boz overexpression was suppressed by raising the level of Lnx-l, but Lnx-l failed to counteract dorsalization caused by mutant Boz lacking a critical motif for Lnx-l binding. Furthermore, dorsalization induced by depletion of Lnx-l was alleviated by attenuation of Boz expression. We conclude that Lnx-l modulates Boz activity to prevent the invasion of ventral regions of the embryo by organizer tissue. These studies introduce a ubiquitin ligase, Lnx-l, as a balancing modulator of axial patterning in the zebrafish embryo.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping