Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: implication of Gli2 and Gli3 as primary mediators of Shh signaling
Embryonic Induction
0301 basic medicine
Mice, Inbred C3H
0303 health sciences
DNA, Complementary
Base Sequence
Molecular Sequence Data
Kruppel-Like Transcription Factors
Gene Expression Regulation, Developmental
Proteins
Mice, Transgenic
Nerve Tissue Proteins
Nervous System
DNA-Binding Proteins
Mice, Inbred C57BL
Repressor Proteins
Mice
03 medical and health sciences
Animals
Hedgehog Proteins
Amino Acid Sequence
Cells, Cultured
DNA Primers
DOI:
10.1242/dev.126.17.3915
Publication Date:
2021-04-26T03:48:17Z
AUTHORS (5)
ABSTRACT
Abstract
Gli family zinc finger proteins are mediators of Sonic hedgehog (Shh) signaling in vertebrates. The question remains unanswered, however, as to how these Gli proteins participate in the Shh signaling pathway. In this study, regulatory activities associated with the Gli2 protein were investigated in relation to the Shh signaling. Although Gli2 acts as a weak transcriptional activator, it is in fact a composite of positive and negative regulatory domains. In cultured cells, truncation of the activation domain in the C- terminal half results in a protein with repressor activity, while removal of the repression domain at the N terminus converts Gli2 into a strong activator. In transgenic mouse embryos, N-terminally truncated Gli2, unlike the full length protein, activates a Shh target gene, HNF3β, in the dorsal neural tube, thus mimicking the effect of Shh signal. This suggests that unmasking of the strong activation potential of Gli2 through modulation of the N-terminal repression domain is one of the key mechanisms of the Shh signaling. A similar regulatory mechanism involving the N-terminal region was also found for Gli3, but not for Gli1. When the Shh signal derived from the notochord is received by the neural plate, the widely expressed Gli2 and Gli3 proteins are presumably converted to their active forms in the ventral cells, leading to activation of transcription of their target genes, including Gli1.
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