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RUNX3, EGR1 and SOX9B Form a Regulatory Cascade Required to Modulate BMP-Signaling during Cranial Cartilage Development in Zebrafish

Authors: Dalcq, Julia; Pasque, Vincent; Ghaye, Aurélie; Larbuisson, Arnaud; Motte, Patrick; Martial, Joseph; Muller, Marc;

RUNX3, EGR1 and SOX9B Form a Regulatory Cascade Required to Modulate BMP-Signaling during Cranial Cartilage Development in Zebrafish

Abstract

The cartilaginous elements forming the pharyngeal arches of the zebrafish derive from cranial neural crest cells. Their proper differentiation and patterning are regulated by reciprocal interactions between neural crest cells and surrounding endodermal, ectodermal and mesodermal tissues. In this study, we show that the endodermal factors Runx3 and Sox9b form a regulatory cascade with Egr1 resulting in transcriptional repression of the fsta gene, encoding a BMP antagonist, in pharyngeal endoderm. Using a transgenic line expressing a dominant negative BMP receptor or a specific BMP inhibitor (dorsomorphin), we show that BMP signaling is indeed required around 30 hpf in the neural crest cells to allow cell differentiation and proper pharyngeal cartilage formation. Runx3, Egr1, Sox9b and BMP signaling are required for expression of runx2b, one of the key regulator of cranial cartilage maturation and bone formation. Finally, we show that egr1 depletion leads to increased expression of fsta and inhibition of BMP signaling in the pharyngeal region. In conclusion, we show that the successive induction of the transcription factors Runx3, Egr1 and Sox9b constitutes a regulatory cascade that controls expression of Follistatin A in pharyngeal endoderm, the latter modulating BMP signaling in developing cranial cartilage in zebrafish.

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Keywords

Male, Follistatin, Time Factors, NGFI-A, ENDODERM FORMATION, C-FOS, General Science & Technology, Science, Oligonucleotides, Biochimie, biophysique & biologie moléculaire, MICE LACKING, Epithelium, Animals, OSTEOCLAST FORMATION, ENCODES, Zebrafish, GENE-EXPRESSION, Early Growth Response Protein 1, Science & Technology, Q, Endoderm, Skull, R, Gene Expression Regulation, Developmental, Cell Differentiation, SOX9 Transcription Factor, FOLLISTATIN, Zebrafish Proteins, Life sciences, Multidisciplinary Sciences, DIFFERENTIATION, Cartilage, Core Binding Factor Alpha 3 Subunit, Pyrimidines, TRANSCRIPTION FACTOR EGR-1, Neural Crest, Bone Morphogenetic Proteins, Sciences du vivant, Science & Technology - Other Topics, Medicine, Pyrazoles, Female, Alcian Blue, Biochemistry, biophysics & molecular biology, Research Article, Signal Transduction

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
48
Top 10%
Top 10%
Top 10%
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gold