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The article discusses research on the involvement of Caenorhabditis elegans homologs nephrocystin-1 and nephrocystin-4 cilia transition zone proteins in chemosensory perception. Nephronophthisis (NPH) is a cystic kidney disorder that causes end-stage renal failure among children. The study identified that nephrocystin-1 and nephrocystin-4 form a complex at cell junctions and focal adhesions. The study's findings suggest that the defects in human NPH patients may not be the result of aberrant ciliogenesis but abnormal cilia-sensory functions.

Defects in cilia are associated with diseases and developmental abnormalities. Proper cilia function is required for sonic hedgehog and PDGFR α signaling in mammals and for insulin-like growth factor (IGF) signaling in Caenorhabditis elegans. However, the role of cilia in these pathways remains unknown. To begin addressing this issue, we are characterizing putative cilia proteins in C. elegans that are predicted to have regulatory rather than structural functions. In this report, we characterized the novel cilia protein T28F3.6 (IFTA-2, intraflagellar transport associated protein 2), which is homologous to the mammalian Rab-like 5 protein. We found that, unlike the intraflagellar transport (IFT) genes, disruption of ifta-2 does not result in overt cilia assembly abnormalities, nor did it cause chemotaxis or osmotic avoidance defects typical of cilia mutants. Rather, ifta-2 null mutants have an extended lifespan phenotype and are defective in dauer formation. Our analysis indicates that these phenotypes result from defects in the DAF-2 (insulin-IGF-1-like) receptor signaling pathway in ciliated sensory neurons. We conclude that IFTA-2 is not a ciliogenic protein but rather is a regulator of specific cilia signaling activities. Interestingly, a mammalian IFTA-2 homolog is also found in cilia, raising the possibility that its function has been conserved during evolution. [ABSTRACT FROM AUTHOR]

Background & Aims: Enteric nervous system (ENS) development requires migration, proliferation, and appropriate neuronal diversification from progenitors to enable normal gastrointestinal (GI) motility. Sox10 deficit causes aganglionosis, modeling Hirschsprung disease, and disrupts ratios of postnatal enteric neurons in proximal ganglionated bowel. How Sox10 deficiency alters ratios of enteric neuron subtypes is unclear. Sox10's prominent expression in enteric neural crest-derived progenitors (ENCP) and lack of this gene in enteric neurons led us to examine Sox10 Dom effects ENS progenitors and early differentiating enteric neurons., Methods: ENS progenitors, developing neurons, and enteric glia were isolated from Sox10 +/+ and Sox10 Dom/+ littermates for single-cell RNA sequencing (scRNA-seq). scRNA-seq data was processed to identify cell type-specific markers, differentially expressed genes, cell fate trajectories, and gene regulatory network activity between genotypes. Hybridization chain reaction (HCR) validated expression changes detected in scRNA-seq., Results: scRNA-seq profiles revealed three neuronal lineages emerging from cycling progenitors via two transition pathways accompanied by elevated activity of Hox gene regulatory networks (GRN) as progenitors transition to neuronal fates. Sox10 Dom/+ scRNA-seq profiles exhibited a novel progenitor cluster, decreased abundance of cells in transitional states, and shifts in cell distributions between two neuronal trajectories. Hoxa6 was differentially expressed in the neuronal lineages impacted in Sox10 Dom/+ mutants and HCR identified altered Hoxa6 expression in early developing neurons of Sox10 Dom/+ ENS., Conclusions: Sox10 Dom/+ mutation shifts enteric neuron types by altering neuronal trajectories during early ENS lineage segregation. Multiple neurogenic transcription factors are reduced in Sox10 Dom/+ scRNA-seq profiles including multiple Hox genes. This is the first report that implicates Hox genes in lineage diversification of enteric neurons.