Biology subjects

Rumley, J. D.

Publications and source records attributed to Rumley, J. D..

3 recordsLinked to original sources

bioRxiv2025

Notch-mediated regulation of β-Catenin-TCF activity instructs anteroposterior neuron positioning in C. elegans

Motor neuron positioning and organization along the neuroaxis is crucial for proper nervous system connectivity and function. In newly hatched C. elegans, the ventral nerve cord contains 22 motor neurons, divided into three classes (DD, DA, and DB), with their cell bodies showing a largely stereotypical positioning and sequential arrangement. However, the mechanisms controlling this precise positioning are not fully understood. Here, we uncover a left-right asymmetry in {beta}-catenin-TCF complex activity that controls motor neuron positioning. Loss of BAR-1/{beta}-catenin or POP-1/TCF causes a shift of motor neuron cell bodies toward the anterior, while loss of PRY-1/Axin shifts them toward the posterior. During embryonic ventral cord morphogenesis, BAR-1 expression is restricted to right-side motor neuron precursors through asymmetric Notch signaling, which promotes PRY-1 expression on the left to degrade BAR-1. Our findings highlight an atypical Notch-mediated regulation of Axin expression and reveal that left-right asymmetry during neuroaxis formation specifies anteroposterior motor neuron placement in the central nerve cord.

developmental biology↗

bioRxiv2021

pop-1/TCF, ref-2/ZIC and T-box factors regulate the development of anterior cells in the C. elegans embryo

Patterning of the anterior-posterior axis is fundamental to animal development. The Wnt pathway plays a major role in this process by activating the expression of posterior genes in animals from worms to humans. This observation raises the question of whether the Wnt pathway or other regulators control the expression of the many anterior-expressed genes. We found that the expression of five anterior-specific genes in Caenorhabditis elegans embryos depends on the Wnt pathway effectors pop-1/TCF and sys-1/{beta}-catenin. We focused further on one of these anterior genes, ref-2/ZIC, a conserved transcription factor expressed in multiple anterior lineages. Live imaging of ref-2 mutant embryos identified defects in cell division timing and position in anterior lineages. Cis-regulatory dissection identified three ref-2 transcriptional enhancers, one of which is necessary and sufficient for anterior-specific expression. This enhancer is activated by the T-box transcription factors TBX-37 and TBX-38, and surprisingly, concatemerized TBX-37/38 binding sites are sufficient to drive anterior-biased expression alone, despite the broad expression of TBX-37 and TBX-38. Taken together, our results highlight the diverse mechanisms used to regulate anterior expression patterns in the embryo. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=175 SRC="FIGDIR/small/472681v6_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@412c25org.highwire.dtl.DTLVardef@b944c2org.highwire.dtl.DTLVardef@1511cedorg.highwire.dtl.DTLVardef@420d4e_HPS_FORMAT_FIGEXP M_FIG C_FIG

genetics↗

bioRxiv2021

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

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 require ceh-13 for expression, 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. Author SummaryHox genes are critical for head-to-tail patterning during embryonic development in all animals. Here we examine the factors that are necessary to turn on two posterior Hox genes, nob-1 and php-3, in the nematode worm, C. elegans. We identified six new transcription factors and three enhancer regions of DNA that can activate expression of nob-1/php-3. Unexpectedly, these activating transcription factors included ceh-13, an anterior Hox gene, and elt-1, a regulator of skin development that is briefly expressed in many cells that do not adopt skin fates, including the cells that express nob-1. Furthermore, the cellular defects we observed in ceh-13 and nob- 1;php-3 mutant embryos indicate that the early embryonic functions of these Hox genes help determine the identity of cells as well as their position within the embryo. Our findings identify new roles for Hox genes in C. elegans and emphasize the ability of transcription factors to contribute to the diversification of cell types and the adoption of specific cell types at different phases of embryonic development.

genetics↗