The Caenorhabditis elegans gene ham-2 links Hox patterning to migration of the HSN motor neuron.
The Caenorhabditis elegans HSN motor neurons permit genetic analysis of neuronal development at single-cell resolution. The egl-5 Hox gene, which patterns the posterior of the embryo, is required for both early (embryonic) and late (larval) development of the HSN. Here we show that ham-2 encodes a zinc finger protein that acts downstream of egl-5 to direct HSN cell migration, an early differentiation event. We also demonstrate that the EGL-43 zinc finger protein, also required for HSN migration, is expressed in the HSN specifically during its migration. In an egl-5 mutant background, the HSN still expresses EGL-43, but expression is no longer down-regulated at the end of the cell's migration. Finally, we find a new role in early HSN differentiation for UNC-86, a POU homeodomain transcription factor shown previously to act downstream of egl-5 in the regulation of late HSN differentiation. In an unc-86; ham-2 double mutant the HSNs are defective in EGL-43 down-regulation, an egl-5-like phenotype that is absent in either single mutant. Thus, in the HSN, a Hox gene, egl-5, regulates cell fate by activating the transcription of genes encoding the transcription factors HAM-2 and UNC-86 that in turn individually control some differentiation events and combinatorially affect others.
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3204, USA.
P D
PD
Baum
C
C
Guenther
C A
CA
Frank
B V
BV
Pham
G
G
Garriga
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D003001:Cloning, Molecular; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005801:Genes, Homeobox / Q000235:genetics*; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D050809:POU Domain Factors; D010641:Phenotype; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics*
D029742:Caenorhabditis elegans Proteins; C118357:HAM-2 protein, C elegans; D015801:Helminth Proteins; D018398:Homeodomain Proteins; D050809:POU Domain Factors; D014157:Transcription Factors; C081539:unc-86 protein, C elegans