Siah2 antagonism of Pard3/JamC modulates Ntn1-Dcc signaling to regulate cerebellar granule neuron germinal zone exit
Year: 2025
Type: article
Abstract: Exiting a germinal zone (GZ) initiates a cascade of events that promote neuronal maturation and circuit assembly. Developing neurons and their progenitors must interpret various niche signals— such as morphogens, guidance molecules, extracellular matrix components, and adhesive cues—to navigate this region. How differentiating neurons integrate and adapt to multiple cellextrinsic niche cues with their cell-intrinsic machinery in exiting a GZ is unknown. We establish cooperation between cell polarity-regulated adhesion and Netrin-1 (Ntn-1) signaling comprises a coincidence detection circuit repelling maturing neurons from their GZ. In this circuit, the Partitioning defective 3 (Pard3) polarity protein and Junctional adhesion molecule-C (JamC) adhesion protein promote, while the Seven in absentia 2 (Siah2) ubiquitin ligase inhibits, Deleted in colorectal cancer (Dcc) receptor surface recruitment to gate differentiation linked repulsion to GZ Ntn-1. These results demonstrate cell polarity as a central integrator of adhesive- and guidance cues cooperating to spur GZ exit.
Source: Nature Communications
Authors: Christophe Laumonnerie, Maleelo Shamambo, Daniel R. Stabley, Tommy L. Lewis, Niraj Trivedi, Danielle Howell, David J. Solecki
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G1514802403, Polarity Signals Coordinate Neuronal Migration and Germinal Zone Exit, G2909414793, Siah2: an E3 ligase organizes polarity and cytoskeletal links in neuron migration, G411266785, G4766096375, G4869702982, G5968154083, G8705713045, G8830688781, G9000027531, Cancer Center Support Grant (CCSG)
OpenAlex ID: W4406150924