The anterior Hox gene ceh-13 and elt-1/GATA activate the posterior Hox genes nob-1 and php-3 to specify posterior lineages in the C. elegans embryo

• Published in: PLoS genetics 2022-05, Vol.18 (5), p.e1010187
• Main Authors: Murray, John Isaac, Preston, Elicia, Crawford, Jeremy P, Rumley, Jonathan D, Amom, Prativa, Anderson, Breana D, Sivaramakrishnan, Priya, Patel, Shaili D, Bennett, Barrington Alexander, Lavon, Teddy D, Hsiao, Erin, Peng, Felicia, Zacharias, Amanda L
• Format: Article
• Language: English
• Subjects: Animal development; Animals; Biology and Life Sciences; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell cycle; Cell division; Daughters; Developmental stages; Embryos; Enhancers; Gastrulation; Gene expression; Gene Expression Regulation, Developmental; Gene regulation; Genes, Homeobox - genetics; Genetic aspects; Genomes; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; HOX gene; Hox genes; Morphogenesis; Physiological aspects; Protein expression; Proteins; Research and Analysis Methods; Software; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1010187

Hox transcription factors play a conserved role in specifying positional identity during animal development, with posterior Hox genes typically repressing the expression of more anterior Hox genes. Here, we dissect the regulation of the posterior Hox genes nob-1 and php-3 in the nematode C. elegans. We show that nob-1 and php-3 are co-expressed in gastrulation-stage embryos in cells that previously expressed the anterior Hox gene ceh-13. This expression is controlled by several partially redundant transcriptional enhancers. These enhancers act in a ceh-13-dependant manner, providing a striking example of an anterior Hox gene positively regulating a posterior Hox gene. Several other regulators also act positively through nob-1/php-3 enhancers, including elt-1/GATA, ceh-20/ceh-40/Pbx, unc-62/Meis, pop-1/TCF, ceh-36/Otx, and unc-30/Pitx. We identified defects in both cell position and cell division patterns in ceh-13 and nob-1;php-3 mutants, suggesting that these factors regulate lineage identity in addition to positional identity. Together, our results highlight the complexity and flexibility of Hox gene regulation and function and the ability of developmental transcription factors to regulate different targets in different stages of development.