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Mena is required for neurulation and commissure formation
L M Lanier1, M A Gates, W Witke
1Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Abstract:
Mammalian enabled (Mena) is a member of a protein family thought to link signal transduction pathways to localized remodeling of the actin cytoskeleton. Mena binds directly to Profilin, an actin-binding protein that modulates actin polymerization. In primary neurons, Mena is concentrated at the tips of growth cone filopodia. Mena-deficient mice are viable; however, axons projecting from interhemispheric cortico-cortical neurons are misrouted in early neonates, and failed decussation of the corpus callosum as well as defects in the hippocampal commissure and the pontocerebellar pathway are evident in the adult. Mena-deficient mice that are heterozygous for a Profilin I deletion die in utero and display defects in neurulation, demonstrating an important functional role for Mena in regulation of the actin cytoskeleton.
Insights
Mammalian enabled (Mena), a protein crucial for actin cytoskeleton remodeling, is essential for proper neuronal axon guidance. Mena deficiency leads to severe developmental defects, including misrouted axons and failed brain commissure formation.
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Mammalian enabled (Mena) is a protein family member implicated in linking signal transduction to actin cytoskeleton remodeling.
- Mena directly binds Profilin, an actin-binding protein that influences actin polymerization.
- In neurons, Mena localizes to growth cone filopodia tips.
Purpose of the Study:
- To investigate the functional role of Mena in neuronal development and actin cytoskeleton regulation.
- To determine the consequences of Mena deficiency on axon guidance and brain development.
Main Methods:
- Analysis of Mena-deficient mice.
- Assessment of axonal projection and brain commissure formation in neonates and adults.
- Examination of developmental defects in mice with combined Mena and Profilin I deficiencies.
Main Results:
- Mena-deficient mice exhibit misrouted axons in cortico-cortical projections.
- Defects in corpus callosum, hippocampal commissure, and pontocerebellar pathways are observed in adult Mena-deficient mice.
- Mice heterozygous for Mena and Profilin I deletions display embryonic lethality and neurulation defects.
Conclusions:
- Mena plays a critical role in regulating the actin cytoskeleton during neuronal development.
- Mena is essential for accurate axon guidance and the formation of major brain commissures.
- The interaction between Mena and Profilin is vital for proper neurulation and embryonic development.