RRC ID 45873
著者 Walton T, Preston E, Nair G, Zacharias AL, Raj A, Murray JI.
タイトル The Bicoid class homeodomain factors ceh-36/OTX and unc-30/PITX cooperate in C. elegans embryonic progenitor cells to regulate robust development.
ジャーナル PLoS Genet
Abstract While many transcriptional regulators of pluripotent and terminally differentiated states have been identified, regulation of intermediate progenitor states is less well understood. Previous high throughput cellular resolution expression studies identified dozens of transcription factors with lineage-specific expression patterns in C. elegans embryos that could regulate progenitor identity. In this study we identified a broad embryonic role for the C. elegans OTX transcription factor ceh-36, which was previously shown to be required for the terminal specification of four neurons. ceh-36 is expressed in progenitors of over 30% of embryonic cells, yet is not required for embryonic viability. Quantitative phenotyping by computational analysis of time-lapse movies of ceh-36 mutant embryos identified cell cycle or cell migration defects in over 100 of these cells, but most defects were low-penetrance, suggesting redundancy. Expression of ceh-36 partially overlaps with that of the PITX transcription factor unc-30. unc-30 single mutants are viable but loss of both ceh-36 and unc-30 causes 100% lethality, and double mutants have significantly higher frequencies of cellular developmental defects in the cells where their expression normally overlaps. These factors are also required for robust expression of the downstream developmental regulator mls-2/HMX. This work provides the first example of genetic redundancy between the related yet evolutionarily distant OTX and PITX families of bicoid class homeodomain factors and demonstrates the power of quantitative developmental phenotyping in C. elegans to identify developmental regulators acting in progenitor cells.
巻・号 11(3)
ページ e1005003
公開日 2015-3-1
DOI 10.1371/journal.pgen.1005003
PII PGENETICS-D-14-02269
PMID 25738873
PMC PMC4349592
MeSH Animals Animals, Genetically Modified Caenorhabditis elegans / embryology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / biosynthesis Caenorhabditis elegans Proteins / genetics* Cell Differentiation / genetics* DNA-Binding Proteins / biosynthesis DNA-Binding Proteins / genetics Embryonic Development / genetics* Gene Expression Regulation, Developmental Homeodomain Proteins / biosynthesis Homeodomain Proteins / genetics* Neurons / cytology Neurons / metabolism Nuclear Proteins / biosynthesis Nuclear Proteins / genetics* Stem Cells / metabolism Transcription Factors / biosynthesis Transcription Factors / genetics*
IF 5.175
引用数 12
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm4063