Siah2 antagonism of Pard3/JamC modulates Ntn1-Dcc signaling to regulate cerebellar granule neuron germinal zone exit
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 navig...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55400-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544556026265600 |
|---|---|
| author | Christophe Laumonnerie Maleelo Shamambo Daniel R. Stabley Tommy L. Lewis Niraj Trivedi Danielle Howell David J. Solecki |
| author_facet | Christophe Laumonnerie Maleelo Shamambo Daniel R. Stabley Tommy L. Lewis Niraj Trivedi Danielle Howell David J. Solecki |
| author_sort | Christophe Laumonnerie |
| collection | DOAJ |
| description | 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 in mouse brains integrate and adapt to multiple cell-extrinsic niche cues with their cell-intrinsic machinery in exiting a GZ is unknown. We establish cooperation between cell polarity-regulated adhesion and Netrin-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 molecule 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 Netrin-1. These results demonstrate cell polarity as a central integrator of adhesive- and guidance cues cooperating to spur GZ exit. |
| format | Article |
| id | doaj-art-f78f9841969d402b982714e3f8b4bd0b |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-f78f9841969d402b982714e3f8b4bd0b2025-01-12T12:30:36ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-024-55400-wSiah2 antagonism of Pard3/JamC modulates Ntn1-Dcc signaling to regulate cerebellar granule neuron germinal zone exitChristophe Laumonnerie0Maleelo Shamambo1Daniel R. Stabley2Tommy L. Lewis3Niraj Trivedi4Danielle Howell5David J. Solecki6Neuronal Cell Biology Division, Department of Developmental Neurobiology, St. Jude Children’s Research HospitalNeuronal Cell Biology Division, Department of Developmental Neurobiology, St. Jude Children’s Research HospitalNeuronal Cell Biology Division, Department of Developmental Neurobiology, St. Jude Children’s Research HospitalAging & Metabolism Program, Oklahoma Medical Research FoundationNeuronal Cell Biology Division, Department of Developmental Neurobiology, St. Jude Children’s Research HospitalNeuronal Cell Biology Division, Department of Developmental Neurobiology, St. Jude Children’s Research HospitalNeuronal Cell Biology Division, Department of Developmental Neurobiology, St. Jude Children’s Research HospitalAbstract 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 in mouse brains integrate and adapt to multiple cell-extrinsic niche cues with their cell-intrinsic machinery in exiting a GZ is unknown. We establish cooperation between cell polarity-regulated adhesion and Netrin-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 molecule 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 Netrin-1. These results demonstrate cell polarity as a central integrator of adhesive- and guidance cues cooperating to spur GZ exit.https://doi.org/10.1038/s41467-024-55400-w |
| spellingShingle | Christophe Laumonnerie Maleelo Shamambo Daniel R. Stabley Tommy L. Lewis Niraj Trivedi Danielle Howell David J. Solecki Siah2 antagonism of Pard3/JamC modulates Ntn1-Dcc signaling to regulate cerebellar granule neuron germinal zone exit Nature Communications |
| title | Siah2 antagonism of Pard3/JamC modulates Ntn1-Dcc signaling to regulate cerebellar granule neuron germinal zone exit |
| title_full | Siah2 antagonism of Pard3/JamC modulates Ntn1-Dcc signaling to regulate cerebellar granule neuron germinal zone exit |
| title_fullStr | Siah2 antagonism of Pard3/JamC modulates Ntn1-Dcc signaling to regulate cerebellar granule neuron germinal zone exit |
| title_full_unstemmed | Siah2 antagonism of Pard3/JamC modulates Ntn1-Dcc signaling to regulate cerebellar granule neuron germinal zone exit |
| title_short | Siah2 antagonism of Pard3/JamC modulates Ntn1-Dcc signaling to regulate cerebellar granule neuron germinal zone exit |
| title_sort | siah2 antagonism of pard3 jamc modulates ntn1 dcc signaling to regulate cerebellar granule neuron germinal zone exit |
| url | https://doi.org/10.1038/s41467-024-55400-w |
| work_keys_str_mv | AT christophelaumonnerie siah2antagonismofpard3jamcmodulatesntn1dccsignalingtoregulatecerebellargranuleneurongerminalzoneexit AT maleeloshamambo siah2antagonismofpard3jamcmodulatesntn1dccsignalingtoregulatecerebellargranuleneurongerminalzoneexit AT danielrstabley siah2antagonismofpard3jamcmodulatesntn1dccsignalingtoregulatecerebellargranuleneurongerminalzoneexit AT tommyllewis siah2antagonismofpard3jamcmodulatesntn1dccsignalingtoregulatecerebellargranuleneurongerminalzoneexit AT nirajtrivedi siah2antagonismofpard3jamcmodulatesntn1dccsignalingtoregulatecerebellargranuleneurongerminalzoneexit AT daniellehowell siah2antagonismofpard3jamcmodulatesntn1dccsignalingtoregulatecerebellargranuleneurongerminalzoneexit AT davidjsolecki siah2antagonismofpard3jamcmodulatesntn1dccsignalingtoregulatecerebellargranuleneurongerminalzoneexit |