Upon arriving at their targets, developing axons cease pathfinding and begin instead to arborize and form synapses. To test whether CNS arborization and synaptogenesis are controlled by Slit-Robo signaling, we followed single retinal ganglion cell (RGC) arbors over time. ast (robo2) mutant and slit1a morphant arbors had more branch tips and greater arbor area and complexity compared to wild-type and concomitantly more presumptive presynaptic sites labeled with YFP-Rab3. Increased arborization in ast was phenocopied by dominant-negative Robo2 expressed in single RGCs and rescued by full-length Robo2, indicating that Robo2 acts cell-autonomously. Time-lapse imaging revealed that ast and slit1a morphant arbors stabilized earlier than wild-type, suggesting a role for Slit-Robo signaling in preventing arbor maturation. Genetic analysis showed that Slit1a acts both through Robo2 and Robo2-independent mechanisms. Unlike previous PNS studies showing that Slits promote branching, our results show that Slits inhibit arborization and synaptogenesis in the CNS.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.neuron.2007.06.034 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Microglia Morphology in the Developing Primate Amygdala and Effects of Early Life Stress.
eNeuro
January 2025
Department of Neuroscience, University of Rochester Medical Center, Rochester, New York 14642
A unique pool of immature glutamatergic neurons in the primate amygdala, known as the paralaminar nucleus (PL), are maturing between infancy and adolescence. The PL is a potential substrate for the steep growth curve of amygdala volume during this developmental period. A microglial component is also embedded among the PL neurons and likely supports local neuronal maturation and emerging synaptogenesis.
View Article and Find Full Text PDFMolecular signature underlying (R)-ketamine rapid antidepressant response on anhedonic-like behavior induced by sustained exposure to stress.
Pharmacol Biochem Behav
December 2024
Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; Department of Pharmacology and Graduate Program in Biological Sciences: Pharmacology and Therapeutics, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Department of Psychiatry and Graduate Program in Psychiatry and Behavioral Sciences, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. Electronic address:
Anhedonia induced by sustained stress exposure is a hallmark symptom of major depressive disorder (MDD) and in rodents, it can be accessed through the sucrose preference test (SPT). (R)-ketamine is a fast-acting antidepressant with less detrimental side effects and abuse liability compared to racemic ketamine. The present study combined high-throughput proteomics and network analysis to identify molecular mechanisms involved in chronic variable stress (CVS)-induced anhedonia and promising targets underlying (R)-ketamine rapid antidepressant response.
View Article and Find Full Text PDFNeuronal splicing of the unmethylated histone H3K4 reader, PHF21A, prevents excessive synaptogenesis.
J Biol Chem
November 2024
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA; Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, Michigan, USA. Electronic address:
Article Synopsis
- PHF21A is a histone-binding protein that works with LSD1 and both proteins are important for neuron-specific splicing, impacting their functions in the brain.
- The study shows that during brain development, PHF21A expression happens before LSD1 expression, leading to reduced activity of their complex and altered methylation processes.
- PHF21A's unique microexon plays a crucial role in preventing excessive synapse formation by moderating LSD1's function, indicating its importance in proper neuronal development.
Unlabelled: A unique pool of immature glutamatergic neurons in the primate amygdala, known as the paralaminar nucleus (PL), are maturing between infancy and adolescence. The PL is a potential substrate for the steep growth curve of amygdala volume during this developmental period. A microglial component is also embedded among the PL neurons, and likely supports local neuronal maturation and emerging synaptogenesis.
View Article and Find Full Text PDFDifferential role of NMDA receptors in hippocampal-dependent spatial memory and plasticity in juvenile male and female rats.
Hippocampus
November 2024
Sagol Department of Neurobiology, Faculty of Natural Sciences, and the Integrated Brain and Behavior Center, University of Haifa, Haifa, Israel.
Early life, or juvenility, stands out as the most pivotal phase in neurodevelopment due to its profound impact over the long-term cognition. During this period, significant changes are made in the brain's connections both within and between different areas, particularly in tandem with the development of more intricate behaviors. The hippocampus is among the brain regions that undergo significant postnatal remodeling, including dendritic arborization, synaptogenesis, the formation of complex spines and neuron proliferation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!