Zebrafish Gli3 functions as both an activator and a repressor in Hedgehog signaling

Autor: Evgenya Popova, Jianchi Feng, Alexander F. Schier, Burcu Guner, Oksana V. Tyurina, Jhumku D. Kohtz, Rolf O. Karlstrom
Rok vydání: 2005
Předmět:
Central Nervous System
Cellular differentiation
Morpholino
Retinal ganglion cells
Eye
chemistry.chemical_compound
Cluster Analysis
Sonic hedgehog
Growth Substances
Zebrafish
In Situ Hybridization
Polymorphism
Single-Stranded Conformational
biology
Gene Expression Regulation
Developmental
Cell Differentiation
Hedgehog signaling pathway
Cell biology
DNA-Binding Proteins
embryonic structures
Morphogen
Signal Transduction
musculoskeletal diseases
animal structures
Microinjections
Cyclopamine
Molecular Sequence Data
Kruppel-Like Transcription Factors
Nerve Tissue Proteins
Retinal ganglion
Zinc Finger Protein Gli3
GLI2
GLI3
C17 cell line
Animals
Hedgehog Proteins
Amino Acid Sequence
Molecular Biology
DNA Primers
Base Sequence
fungi
Sequence Analysis
DNA
Cell Biology
Oligonucleotides
Antisense
Zebrafish Proteins
biology.organism_classification
chemistry
Trans-Activators
Cancer research
biology.protein
Sequence Alignment
Gli
Transcription Factors
Developmental Biology
Zdroj: Developmental Biology. 277:537-556
ISSN: 0012-1606
DOI: 10.1016/j.ydbio.2004.10.003
Popis: Hedgehog (Hh) signaling regulates cell differentiation and patterning in a wide variety of embryonic tissues. In vertebrates, at least three Gli transcription factors (Gli1, Gli2, and Gli3) are involved in Hh signal transduction. Comparative studies have revealed divergent requirements for Gli1 and Gli2 in zebrafish and mouse. Here, we address the question of whether Gli3 function has also diverged in zebrafish and analyze the regulatory interactions between Hh signaling and Gli activity. We find that zebrafish Gli3 has an early function as an activator of Hh target genes that overlaps with Gli1 activator function in the ventral neural tube. In vitro reporter analysis shows that Gli3 cooperates with Gli1 to activate transcription in the presence of high concentrations of Hh. During late somitogenesis stages, Gli3 is required as a repressor of the Hh response. Gli3 shares this repressor activity with Gli2 in the dorsal spinal cord, hindbrain, and midbrain, but not in the forebrain. Consistently, zebrafish Gli3 blocks Gli1-mediated activation of a reporter gene in the absence of Hh in vitro. In the eye, Gli3 is also required for proper ath5 expression and the differentiation of retinal ganglion cells (RGCs). These results reveal a conserved role for Gli3 in vertebrate development and uncover novel regional functions and regulatory interactions among gli genes.
Databáze: OpenAIRE
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