NDR kinase SAX-1 controls dendrite branch-specific elimination during neuronal remodeling in C. elegans

Neuronal remodeling is crucial for proper nervous system development and function. Despite significant advances, the underlying mechanisms that govern this process remain poorly understood. Here, we adapted C. elegans IL2 sensory neurons as a model system to study developmental and organismal stress-associated dendrite remodeling. Upon entering developmental diapause, IL2 dendrites grow a complex dendritic arbor, which is later pruned when reproductive development resumes. We identified unexpected specificity in the pruning process, with distinct genetic requirements to direct branch-specific elimination of secondary, tertiary, and quaternary branches. The serine/threonine kinase SAX-1/NDR promotes elimination of secondary and tertiary, but not quaternary, dendrites. SAX-1 functions with its conserved interactors SAX-2/Furry and MOB-2 in the removal of both dendritic branches. The guanine-nucleotide exchange factor RABI-1/Rabin8 and the small GTPase RAB-11.2 mediate the elimination of secondary branches with SAX-1, but their effect on tertiary branches is minimal. Consistent with the known roles of RABI-1 and RAB-11.2 in regulating membrane dynamics, we find that SAX-1 promotes endocytosis during remodeling. Together, our findings reveal distinct mechanisms for dendrite branch-specific elimination during neuronal remodeling.

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Publication Details

Journal
The EMBO Journal
Published
2026-06-27
DOI
https://doi.org/10.1038/s44318-026-00841-w
Primary Topic
Genetics, Aging, and Longevity in Model Organisms
Type
article
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article

NDR kinase SAX-1 controls dendrite branch-specific elimination during neuronal remodeling in C. elegans

Shaul Yogev, Pedro J Diaz Delgado
The EMBO Journal
Genetics, Aging, and Longevity in Model Organisms
article

NDR kinase SAX-1 controls dendrite branch-specific elimination during neuronal remodeling in C. elegans

Shaul Yogev, Pedro J Diaz Delgado
article en

Abstract

Neuronal remodeling is crucial for proper nervous system development and function. Despite significant advances, the underlying mechanisms that govern this process remain poorly understood. Here, we adapted C. elegans IL2 sensory neurons as a model system to study developmental and organismal stress-associated dendrite remodeling. Upon entering developmental diapause, IL2 dendrites grow a complex dendritic arbor, which is later pruned when reproductive development resumes. We identified unexpected specificity in the pruning process, with distinct genetic requirements to direct branch-specific elimination of secondary, tertiary, and quaternary branches. The serine/threonine kinase SAX-1/NDR promotes elimination of secondary and tertiary, but not quaternary, dendrites. SAX-1 functions with its conserved interactors SAX-2/Furry and MOB-2 in the removal of both dendritic branches. The guanine-nucleotide exchange factor RABI-1/Rabin8 and the small GTPase RAB-11.2 mediate the elimination of secondary branches with SAX-1, but their effect on tertiary branches is minimal. Consistent with the known roles of RABI-1 and RAB-11.2 in regulating membrane dynamics, we find that SAX-1 promotes endocytosis during remodeling. Together, our findings reveal distinct mechanisms for dendrite branch-specific elimination during neuronal remodeling.

The EMBO Journal
Yale University (US)
Openalex Percentile: Top 10%
Genetics, Aging, and Longevity in Model Organisms
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