TY - JOUR
T1 - Sonic hedgehog differentially regulates expression of GLI and GLI3 during limb development
AU - Marigo, Valeria
AU - Johnson, Randy L.
AU - Vortkamp, Andrea
AU - Tabin, Clifford J.
N1 - Funding Information:
We thank Olivia E. Orozco and John Lin for help in sequencing, Phil Ingham for VP16 activator domain and sharing information prior to publication, and Matt Scott for fruitful discussion of the data. We are grateful to members of the Tabin and Cepko lab for helpful comments on the manuscript. This work was supported by grants from the Human Frontier Science Program and the National Institutes of Health.
PY - 1996/11/25
Y1 - 1996/11/25
N2 - Sonic hedgehog is a secreted factor regulating patterning of the anterior-posterior axis in the developing limb. The signaling pathway mediating the transduction of the signal is still poorly understood. In Drosophila several genes are known to act downstream of hedgehog, the fly homolog of Sonic hedgehog. An important gene epistatic to hedgehog is cubitus interruptus, which encodes the fly homolog of a family of vertebrate putative transcription factors, the GLI genes. We have isolated two members of the GLI family from chick, called GLI and GLI3. Their expression patterns in a variety of tissues during embryogenesis suggest that these genes may be targets of the Sonic hedgehog signal. We demonstrate that the two GLI genes are differentially regulated by Sonic hedgehog during limb development. Sonic hedgehog up-regulates GLI transcription, while down-regulating GLI3 expression in the mesenchymal cells of the developing limb bud. Finally, we demonstrate that an activated form of GLI can induce expression of Patched, a known target of Sonic hedgehog, thus implicating GLI as a key transcription factor in the vertebrate hedgehog signaling pathway. In conjunction with evidence from a mouse GLi3 mutant, our data suggest that GLI and GLI3 may have taken two different functions of their Drosophila homolog cubitus interruptus.
AB - Sonic hedgehog is a secreted factor regulating patterning of the anterior-posterior axis in the developing limb. The signaling pathway mediating the transduction of the signal is still poorly understood. In Drosophila several genes are known to act downstream of hedgehog, the fly homolog of Sonic hedgehog. An important gene epistatic to hedgehog is cubitus interruptus, which encodes the fly homolog of a family of vertebrate putative transcription factors, the GLI genes. We have isolated two members of the GLI family from chick, called GLI and GLI3. Their expression patterns in a variety of tissues during embryogenesis suggest that these genes may be targets of the Sonic hedgehog signal. We demonstrate that the two GLI genes are differentially regulated by Sonic hedgehog during limb development. Sonic hedgehog up-regulates GLI transcription, while down-regulating GLI3 expression in the mesenchymal cells of the developing limb bud. Finally, we demonstrate that an activated form of GLI can induce expression of Patched, a known target of Sonic hedgehog, thus implicating GLI as a key transcription factor in the vertebrate hedgehog signaling pathway. In conjunction with evidence from a mouse GLi3 mutant, our data suggest that GLI and GLI3 may have taken two different functions of their Drosophila homolog cubitus interruptus.
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U2 - 10.1006/dbio.1996.0300
DO - 10.1006/dbio.1996.0300
M3 - Article
C2 - 8948590
AN - SCOPUS:0030601955
SN - 0012-1606
VL - 180
SP - 273
EP - 283
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -