Identification of a distant cis‐regulatory element controlling pharyngeal arch‐specific expression of zebrafish gdf6a/radar
Identification of a distant cis‐regulatory element controlling pharyngeal arch‐specific expression of zebrafish gdf6a/radar
AbstractSkeletal formation is an essential and intricately regulated part of vertebrate development. Humans and mice deficient in growth and differentiation factor 6 (Gdf6) have numerous skeletal abnormalities, including joint fusions and cartilage reductions. The expression of Gdf6 is dynamic and in part regulated by distant evolutionarily conserved cis‐regulatory elements. radar/gdf6a is a zebrafish ortholog of Gdf6 and has an essential role in embryonic patterning. Here, we show that radar is transcribed in the cells surrounding and between the developing cartilages of the ventral pharyngeal arches, similar to mouse Gdf6. A 312 bp evolutionarily conserved region (ECR5), 122 kilobases downstream, drives expression in a pharyngeal arch‐specific manner similar to endogenous radar/gdf6a. Deletion analysis identified a 78 bp region within ECR5 that is essential for transgene activity. This work illustrates that radar is regulated in the pharyngeal arches by a distant conserved element and suggests radar has similar functions in skeletal development in fish and mammals. Developmental Dynamics 239:1047–1060, 2010. © 2010 Wiley‐Liss, Inc.
- University of Oxford United Kingdom
- Meharry Medical College United States
- Wellcome Centre for Human Genetics United Kingdom
- Vanderbilt University United States
Embryo, Nonmammalian, Base Sequence, Molecular Sequence Data, Gene Expression Regulation, Developmental, Sequence Homology, Growth Differentiation Factor 6, Regulatory Sequences, Nucleic Acid, Zebrafish Proteins, Takifugu, Animals, Genetically Modified, Mice, Branchial Region, Organ Specificity, Animals, Humans, Cloning, Molecular, Zebrafish
Embryo, Nonmammalian, Base Sequence, Molecular Sequence Data, Gene Expression Regulation, Developmental, Sequence Homology, Growth Differentiation Factor 6, Regulatory Sequences, Nucleic Acid, Zebrafish Proteins, Takifugu, Animals, Genetically Modified, Mice, Branchial Region, Organ Specificity, Animals, Humans, Cloning, Molecular, Zebrafish
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