RRC ID 2469
Author Vanderlaan G, Tyurina OV, Karlstrom RO, Chandrasekhar A.
Title Gli function is essential for motor neuron induction in zebrafish.
Journal Dev Biol
Abstract The Gli family of zinc-finger transcription factors mediates Hedgehog (Hh) signaling in all vertebrates. However, their roles in ventral neural tube patterning, in particular motor neuron induction, appear to have diverged across species. For instance, cranial motor neurons are essentially lost in zebrafish detour (gli1(-)) mutants, whereas motor neuron development is unaffected in mouse single gli and some double gli knockouts. Interestingly, the expression of some Hh-regulated genes (ptc1, net1a, gli1) is mostly unaffected in the detour mutant hindbrain, suggesting that other Gli transcriptional activators may be involved. To better define the roles of the zebrafish gli genes in motor neuron induction and in Hh-regulated gene expression, we examined these processes in you-too (yot) mutants, which encode dominant repressor forms of Gli2 (Gli2(DR)), and following morpholino-mediated knockdown of gli1, gli2, and gli3 function. Motor neuron induction at all axial levels was reduced in yot (gli2(DR)) mutant embryos. In addition, Hh target gene expression at all axial levels except in rhombomere 4 was also reduced, suggesting an interference with the function of other Glis. Indeed, morpholino-mediated knockdown of Gli2(DR) protein in yot mutants led to a suppression of the defective motor neuron phenotype. However, gli2 knockdown in wild-type embryos generated no discernable motor neuron phenotype, while gli3 knockdown reduced motor neuron induction in the hindbrain and spinal cord. Significantly, gli2 or gli3 knockdown in detour (gli1(-)) mutants revealed roles for Gli2 and Gli3 activator functions in ptc1 expression and spinal motor neuron induction. Similarly, gli1 or gli3 knockdown in yot (gli2(DR)) mutants resulted in severe or complete loss of motor neurons, and of ptc1 and net1a expression, in the hindbrain and spinal cord. In addition, gli1 expression was greatly reduced in yot mutants following gli3, but not gli1, knockdown, suggesting that Gli3 activator function is specifically required for gli1 expression. These observations demonstrate that Gli activator function (encoded by gli1, gli2, and gli3) is essential for motor neuron induction and Hh-regulated gene expression in zebrafish.
Volume 282(2)
Pages 550-70
Published 2005-6-15
DOI 10.1016/j.ydbio.2005.04.010
PII S0012-1606(05)00226-5
PMID 15890329
PMC PMC2219918
MeSH Animals Embryonic Induction / physiology* Gene Expression Regulation, Developmental* Genotype Hedgehog Proteins Immunohistochemistry Membrane Proteins Motor Neurons / physiology* Multigene Family / genetics Mutation / genetics Oligonucleotides, Antisense Patched Receptors Patched-1 Receptor Receptors, Cell Surface / metabolism Signal Transduction / physiology* Trans-Activators / metabolism* Transcription Factors / genetics* Veratrum Alkaloids Zebrafish / embryology* Zebrafish / metabolism Zebrafish Proteins / genetics* Zinc Finger Protein Gli2
IF 2.896
Times Cited 38
Zebrafish rw0