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Protocadherin Celsr3 is crucial in axonal tract development
Fadel Tissir1, Isabelle Bar, Yves Jossin
1Developmental Neurobiology Unit, University of Louvain Medical School, 73, avenue Mounier, Box DENE7382, B-1200 Brussels, Belgium.
Nature Neuroscience
|March 22, 2005
Summary
The Celsr3 gene is crucial for developing major axonal tracts in the mammalian central nervous system (CNS). Its inactivation leads to significant axonal development anomalies, highlighting protocadherins
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Axonal tract development in the embryonic central nervous system (CNS) is vital for neural connections.
- This development is influenced by various genetic and microenvironmental factors.
- Protocadherins are implicated in cellular development, but their role in mammalian CNS axonal development was unclear.
Purpose of the Study:
- To investigate the role of Celsr3, a seven-pass protocadherin, in mammalian CNS axonal development.
- To determine if protocadherins play a role in forming major axonal fascicles.
- To explore the connection between Celsr3, Frizzled3 (Fzd3), and planar cell polarity (PCP) pathways in neural development.
Main Methods:
- Generation and analysis of Celsr3-inactivated mice.
- Observation of axonal tract formation and morphology in the CNS.
- Comparison of neural phenotypes with those of Fzd3-inactivation.
Main Results:
- Mice lacking Celsr3 exhibited significant and selective anomalies in several major axonal fascicles.
- This finding implicates protocadherins in mammalian CNS axonal development.
- The neural phenotype in Celsr3 mutants resembled that of Fzd3 mutants, suggesting a functional link.
Conclusions:
- Celsr3 is essential for the proper development of axonal tracts in the mammalian CNS.
- A genetic pathway similar to the one controlling planar cell polarity (PCP) is critical for establishing the axonal blueprint.
- Celsr3 and Fzd3 may function synergistically during brain development.