zag-1, a Zn-finger homeodomain transcription factor controlling neuronal differentiation and axon outgrowth in C. elegans.
The nervous system consists of diverse subtypes of neurons, whose identities must be specified during development. One important aspect of the differentiation program of neurons is the expression of the appropriate set of genes controlling axon pathway selection. We have identified a novel Znfinger/homeodomain containing transcription factor, zag-1, required for particular aspects of axonal pathfinding. In zag-1 mutants, motorneuron commissures either branch prematurely or fail to branch at the correct point. Ventral cord interneurons show defects in the guidance towards the ventral cord and also in the ventral cord. Several neurons misexpress differentiation markers, including glutamate receptor subunits and chemosensory receptors. zag-1 is expressed transiently in embryonic and postembryonic neurons during differentiation as well as in some mesodermal tissues. Null mutants of zag-1 are unable to swallow food and die as L1 larvae with a starved appearance, indicating that zag-1 has an additional role in pharynx development. The vertebrate homolog, deltaEF1, is highly conserved and known to act as transcriptional repressor in various tissues. Our data indicate that zag-1 also acts as transcriptional repressor controlling important aspects of terminal differentiation of neurons.
Wacker
Irene
I
Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.
Schwarz
Valentin
V
Hedgecock
Edward M
EM
Hutter
Harald
H
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000235:genetics / 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; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008648:Mesoderm / Q000502:physiology; 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; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
D029742:Caenorhabditis elegans Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C477509:ZAG-1 protein, C elegans