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Published on: June 9, 2021
Lgr5 Marks Post-Mitotic, Lineage Restricted Cerebellar Granule Neurons during Postnatal Development
Tyler E Miller1, Jun Wang2, Kumar Sukhdeo1
1Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) marks cerebellar granule neurons during their maturation. This Wnt signaling co-receptor is transiently expressed in the postnatal cerebellum, revealing a novel role in regulating post-mitotic cells.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Wnt signaling is crucial for stem cell self-renewal and differentiation.
- Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is a Wnt signaling co-receptor identifying proliferative stem cells in various tissues.
- Lgr5 expression in the brain, particularly during neural development, remains largely uncharacterized.
Purpose of the Study:
- To investigate the expression and role of Lgr5 in the developing and adult brain.
- To characterize Lgr5's temporal and spatial expression patterns in the cerebellum.
- To explore the function of Lgr5 in cerebellar granule neuron (CGN) maturation and Wnt signaling.
Main Methods:
- Utilized a transgenic reporter mouse model for in vivo Lgr5 expression analysis.
- Employed lineage tracing techniques to track Lgr5-marked cells.
- Analyzed Lgr5 expression during postnatal cerebellar development and synaptogenesis.
Main Results:
- Lgr5 is expressed in the postnatal cerebellum, specifically during the maturation and synaptogenesis of cerebellar granule neurons (CGNs).
- Lgr5 expression was temporally restricted to the CGN maturation phase within the internal granule layer and absent in the adult brain.
- Lgr5-identified cells were lineage-restricted, post-mitotic, and long-lived, with paracrine R-spondin secretion evolving during CGN maturation.
Conclusions:
- Lgr5 plays a specific role in the maturation phase of cerebellar granule neurons.
- The findings suggest a novel function for Lgr5 in regulating post-mitotic cells within the developing cerebellum.
- This study provides new insights into Wnt signaling regulation during cerebellar development.
