An unusual Zn-finger/FH2 domain protein controls a left/right asymmetric neuronal fate decision in C. elegans.
Gene regulatory networks that control the terminally differentiated state of a cell are, by and large, only superficially understood. In a mutant screen aimed at identifying regulators of gene batteries that define the differentiated state of two left/right asymmetric C. elegans gustatory neurons, ASEL and ASER, we have isolated a mutant, fozi-1, with a novel mixed-fate phenotype, characterized by de-repression of ASEL fate in ASER. fozi-1 codes for a protein that functions in the nucleus of ASER to inhibit the expression of the LIM homeobox gene lim-6, neuropeptide-encoding genes and putative chemoreceptors of the GCY gene family. The FOZI-1 protein displays a highly unusual domain architecture, that combines two functionally essential C2H2 zinc-finger domains, which are probably involved in transcriptional regulation, with a formin homology 2 (FH2) domain, normally found only in cytosolic regulators of the actin cytoskeleton. We demonstrate that the FH2 domain of FOZI-1 has lost its actin polymerization function but maintains its phylogenetically ancient ability to homodimerize. fozi-1 genetically interacts with several transcription factors and micro RNAs in the context of specific regulatory network motifs. These network motifs endow the system with properties that provide insights into how cells adopt their stable terminally differentiated states.
Johnston
Robert J
RJ
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, 701 W. 168th Street, New York, NY 10032, USA.
Copeland
John W
JW
Fasnacht
Marc
M
Etchberger
John F
JF
Liu
Jun
J
Honig
Barry
B
Hobert
Oliver
O
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D003001:Cloning, Molecular; D017931:DNA Primers; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype; D017386:Sequence Homology, Amino Acid; D013649:Taste; D014157:Transcription Factors; D016335:Zinc Fingers
D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D014157:Transcription Factors