RRC ID |
45873
|
Author |
Walton T, Preston E, Nair G, Zacharias AL, Raj A, Murray JI.
|
Title |
The Bicoid class homeodomain factors ceh-36/OTX and unc-30/PITX cooperate in C. elegans embryonic progenitor cells to regulate robust development.
|
Journal |
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.
|
Volume |
11(3)
|
Pages |
e1005003
|
Published |
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
|
Times Cited |
12
|
WOS Category
|
GENETICS & HEREDITY
|
Resource |
C.elegans |
tm4063 |