Biology subjects

Roenspies, T.

Publications and source records attributed to Roenspies, T..

4 recordsLinked to original sources

bioRxiv2025

Nuclear hormone receptor regulation of Caudal mediates ventral nerve cord assembly in C. elegans.

The regulatory network governed by CDX/Caudal family transcription factors plays critical roles in shaping embryonic neural development. In C. elegans, we found that proper expression of pal-1, the C. elegans Caudal homologue, is required for correct positioning of motor neuron cell bodies in the first larval stage ventral nerve cord (VNC). We identified an upstream regulatory region within the pal-1 promoter that drives pal-1 expression in a subset of DD and DA neuronal progenitors. We also show that SEX-1, a nuclear hormone receptor, is required for motor neuron positioning in the VNC. Loss of sex-1 results in neuronal positioning defects similar to those observed in pal-1 mutants. This is in part due to a requirement for SEX-1 in promoting pal-1 expression in DD and DA neuronal progenitors during VNC assembly. Double mutant analysis further suggests that sex-1 also has pal-1-independent functions. Together, these findings define a transcriptional hierarchy in which the SEX-1 nuclear hormone receptor regulates the tissue-specific activity of PAL-1 to promote proper motor neuron positioning in the VNC and highlight a conserved role for NHR and CDX/Caudal family proteins in central nerve cord formation. Highlights- PAL-1 is required for proper neuron cell body positioning in the ventral nerve cord (VNC) in newly hatched worms. - An upstream promoter element controls the expression of pal-1 in DD and DA neurons. - The nuclear hormone receptor SEX-1 is required for proper neuron positioning in the VNC. - SEX-1 regulates PAL-1 expression in DD and DA neurons.

developmental biology↗

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↗

bioRxiv2024

VNC-Dist: A machine learning-based tool for quantification of neuronal positioning in the ventral nerve cord of C. elegans

The C. elegans ventral nerve cord (VNC) provides a simple model for investigating the developmental mechanisms involved in neuronal positioning and organization. The VNC of newly hatched larvae contains a set of 22 motoneurons organized into three distinct classes (DD, DA, and DB) that show consistent positioning and arrangement. This organization arises from the action of multiple convergent genetic pathways, which are poorly understood. To better understand these pathways, accurate and efficient methods for quantifying motoneuron cell body positions within large microscopy datasets are required. Here, we present VNC-Dist (Ventral Nerve Cord Distances), a software toolkit that replaces manual measurements with a faster and more accurate computer-assisted approach, combining machine learning and other tools, to quantify neuron cell body positions in the VNC. The VNC-Dist pipeline integrates several components: manual neuron cell body localization using Fijis multipoint tool, deep learning-based worm segmentation with modified Segment Anything Model (SAM), accurate spline-based measurements of neuronal distances along the VNC, and built-in tools for statistical analysis and graphing. To demonstrate the robustness and versatility of VNC-Dist, we applied it to several genetic mutants known to disrupt neuronal positioning in the VNC. This toolbox will enable batch acquisition and analysis of large datasets across genotypes, thereby advancing investigations into the cellular and molecular mechanisms that govern VNC neuronal positioning and arrangement.

developmental biology↗

bioRxiv2024

IPPK-1 and IP6 contribute to ventral nerve cord assembly in C. elegans

Inositol phosphates (IPs) are essential for the development and function of the nervous system. Loss-of-function studies, which demonstrate the importance of specific IP isomers, show their critical role in proper neural tube formation. In this study, we show that inositol pentakisphosphate 2-kinase (IPPK-1), the kinase that phosphorylates IP5 to generate IP6, is involved in assembling the ventral nerve cord (VNC) in C. elegans. We show that mutations in ippk-1 lead to the mispositioning of motor neurons along the VNC of newly hatched larvae. These positioning defects reflect disruption of VNC assembly during embryogenesis, as VNC neuronal progenitors in ippk-1 embryos display a more compact organization after arising on the left and right sides of the embryo, delays in rosette-mediated convergent extension, and defects in cell intercalation. We further show that injection of exogenous IP6 into the gonads of ippk-1 mutants can rescue both embryonic and neuron positioning defects. Our findings indicate that IP isomers, particularly IP6, are important for ventral nerve cord formation in C. elegans. Along with their role in neural tube formation in vertebrates, these results suggests that IP isomers play an ancient role in central nerve cord development. Highlights- ipmk-1 and ippk-1 mutants display neuron position defects in the ventral nerve cord (VNC). - ippk-1 mutants display disorganization in VNC neuronal progenitors during VNC assembly. - IPPK-1 is involved in convergent extension during VNC formation. - Exogenous IP6 rescues larval and embryonic defects in ippk-1 mutants.

developmental biology↗