Biphasic wnt8a expression is achieved through interactions of multiple regulatory inputs
- Authors
- Narayanan, A., and Lekven, A.C.
- ID
- ZDB-PUB-120409-4
- Date
- 2012
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 241(6): 1062-1075 (Journal)
- Registered Authors
- Lekven, Arne
- Keywords
- wnt8a, mesoderm induction, vertebrate, zebrafish, Nodal, Brachyury, Zbtb4, embryonic margin, transcriptional regulation, enhancer
- MeSH Terms
-
- Regulatory Elements, Transcriptional/genetics
- Regulatory Elements, Transcriptional/physiology*
- Zebrafish/embryology*
- Zebrafish/metabolism
- Binding Sites/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Promoter Regions, Genetic/genetics
- Body Patterning/physiology*
- Base Sequence
- Wnt Proteins/genetics
- Wnt Proteins/metabolism*
- Cytoskeletal Proteins/genetics
- Cytoskeletal Proteins/metabolism*
- Animals
- Nodal Protein/metabolism
- Mesoderm/embryology
- Mesoderm/metabolism
- Gastrula/embryology*
- Gastrula/metabolism
- T-Box Domain Proteins/metabolism
- Molecular Sequence Data
- Gene Expression Regulation, Developmental/genetics
- Gene Expression Regulation, Developmental/physiology*
- Fetal Proteins
- Species Specificity
- DNA Primers/genetics
- Smegmamorpha/embryology
- Smegmamorpha/metabolism
- PubMed
- 22473868 Full text @ Dev. Dyn.
Background:
Vertebrate axis development depends upon wnt8a transcription in a dynamic pool of mesoderm progenitors at the posterior pole of the gastrulating embryo. The transcriptional mechanisms controlling wnt8a expression are not understood, but previous studies identified two phases of wnt8a expression in zebrafish: Nodal-dependent activation during early gastrulation (phase I) and No tail (Ntl)-dependent regulation from mid gastrula stages (phase II).
Results:
We identified two upstream cis-regulatory regions, proximal and distal, each of which possesses a promoter. The proximal regulatory region contains a margin-specific enhancer that is required for both the Nodal and Ntl responses. Phase I expression requires Nodal activation of the margin enhancer in combination with the transcription factor Zbtb4 and the distal regulatory region. Phase II expression requires Ntl regulation of the margin enhancer in the context of the proximal regulatory region. An additional mechanism is required to ensure the transition from phase I to phase II regulation. Analysis of stickleback wnt8a suggests this mechanism of regulation may be conserved.
Conclusion:
The seemingly simple wnt8a expression pattern reflects complex interactions of multiple regulatory inputs.