PUBLICATION
Hindbrain patterning requires fine-tuning of early krox20 transcription by Sprouty 4
- Authors
- Labalette, C., Bouchoucha, Y.X., Wassef, M.A., Gongal, P.A., Le Men, J., Becker, T., Gilardi-Hebenstreit, P., and Charnay, P.
- ID
- ZDB-PUB-110103-6
- Date
- 2011
- Source
- Development (Cambridge, England) 138(2): 317-326 (Journal)
- Registered Authors
- Becker, Thomas S., Bouchoucha, Yassine, Charnay, Patrick, Gilardi-Hebenstreit, Pascale, Gongal, Patricia, Labalette, Charlotte, Le Men, Johan
- Keywords
- FGF, Segmentation, Rhombomere, Feedback loop, Zebrafish
- MeSH Terms
-
- Nerve Tissue Proteins/genetics
- Nerve Tissue Proteins/metabolism*
- Signal Transduction
- Oncogene Proteins/genetics
- Oncogene Proteins/metabolism
- DNA Primers/genetics
- Gene Expression Regulation, Developmental
- Feedback, Physiological
- Base Sequence
- Fibroblast Growth Factors/metabolism
- MafB Transcription Factor/genetics
- MafB Transcription Factor/metabolism
- Body Patterning/genetics
- Body Patterning/physiology
- Enhancer Elements, Genetic
- Binding Sites/genetics
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Rhombencephalon/embryology*
- Rhombencephalon/metabolism*
- Early Growth Response Protein 2/genetics*
- Avian Proteins/genetics
- Avian Proteins/metabolism
- Animals
- Chick Embryo
- Transcription, Genetic
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Multigene Family
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 21177344 Full text @ Development
Citation
Labalette, C., Bouchoucha, Y.X., Wassef, M.A., Gongal, P.A., Le Men, J., Becker, T., Gilardi-Hebenstreit, P., and Charnay, P. (2011) Hindbrain patterning requires fine-tuning of early krox20 transcription by Sprouty 4. Development (Cambridge, England). 138(2):317-326.
Abstract
Vertebrate hindbrain segmentation is an evolutionarily conserved process that involves a complex interplay of transcription factors and signalling pathways. Fibroblast growth factor (FGF) signalling plays a major role, notably by controlling the expression of the transcription factor Krox20 (Egr2), which is required for the formation and specification of two segmental units: rhombomeres (r) 3 and 5. Here, we explore the molecular mechanisms downstream of FGF signalling and the function of Sprouty 4 (Spry4), a negative-feedback regulator of this pathway, in zebrafish. We show that precise modulation of FGF signalling by Spry4 is required to determine the appropriate onset of krox20 transcription in r3 and r5 and, ultimately, rhombomere size in the r3-r5 region. FGF signalling acts by modulating the activity of krox20 initiator enhancer elements B and C; in r5, we show that this regulation is mediated by direct binding of the transcription factor MafB to element B. By contrast, FGF signalling does not control the krox20 autoregulatory element A, which is responsible for amplification and maintenance of krox20 expression. Therefore, early krox20 transcription sets the blueprint for r3-r5 patterning. This work illustrates the necessity for fine-tuning in a common and fundamental patterning process, based on a bistable cell-fate choice involving the coupling of an extracellular gradient with a positive-feedback loop. In this mode of patterning, precision and robustness can be achieved by the introduction of a negative-feedback loop, which, in the hindbrain, is mediated by Spry4.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping