C. elegans ZAG-1, a Zn-finger-homeodomain protein, regulates axonal development and neuronal differentiation.
Neurons acquire distinct cell identities and implement differential gene programs to generate their appropriate neuronal attributes. On the basis of position, axonal structure and synaptic connectivity, the 302 neurons of the nematode Ceanorhabditis elegans are divided into 118 classes. The development and differentiation of many neurons require the gene zag-1, which encodes a deltaEF1/ZFH-1 Zn-finger-homeodomain protein. zag-1 mutations cause misexpression of neuron-specific genes, block formation of stereotypic axon branches, perturb neuronal migrations, and induce various axon-guidance, fasciculation and branching errors. A zag-1-GFP translational reporter is expressed transiently in most or all neurons during embryogenesis and in select neurons during the first larval stage. Analysis of the zag-1 promoter reveals that zag-1 is expressed in neurons and specific muscles, and that ZAG-1 directly represses its own expression. zag-1 activity also downregulates expression of genes involved in either the synthesis or reuptake of serotonin, dopamine and GABA. We propose that ZAG-1 acts as a transcriptional repressor to regulate multiple, discrete, neuron-specific aspects of terminal differentiation, including cell migration, axonal development and gene expression.
Clark
Scott G
SG
Molecular Neurobiology Program, Department of Pharmacology, Skirball Institute, NYU School of Medicine, New York, NY 10016, USA.
Chiu
Catherine
C
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology*; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000235:genetics / Q000378:metabolism; D030781:Organisms, Genetically Modified; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D016335:Zinc Fingers
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C477509:ZAG-1 protein, C elegans; C081010:zfh1 protein, Drosophila