Unaltered expression of Bcl-2 and TAG-1/axonin-1 precedes sensory apoptosis in Brn3a knockout mice
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Updated: Sep 27, 2026
Ex Utero Electroporation and Organotypic Slice Culture of Mouse Hippocampal Tissue
Published on: March 4, 2015
S Raisa Eng1, Serguei Kozlov, Eric E Turner
1Department of Psychiatry, University of California, San Diego, La Jolla 92093-0603, USA.
Abstract:
Mice lacking the POU-domain transcription factor Brn3a exhibit growth defects in trigeminal axons, undergo extensive sensory cell death in late gestation, and die at birth. Based on tissue culture studies, the mediator of apoptosis Bcl-2 has been suggested as a target of Brn3a regulation which could affect sensory viability in these mice. In addition, Bcl-2 and the neural cell adhesion molecule TAG-1/axonin-1 have both been implicated in sensory axon guidance. In this study we examined wild-type and Brn3a knockout embryos for alterations in the expression of these genes. Trigeminal ganglia were harvested from embryonic day 13.5 mouse embryos, and Bcl-2 and TAG-1 expression were measured by RT-PCR. TAG-1 expression was also examined in the embryonic trigeminal and dorsal root ganglia by immunohistochemistry. The developing trigeminal ganglia of Brn3a knockout mice exhibit similar levels of Bcl-2 and TAG-1 mRNA expression. Immunohistochemical staining of TAG-1 also appeared to be quantitatively similar in the sensory axons of wild-type and knockout embryos. It is unlikely that Bcl-2 is a regulatory target of Brn3a, or that either of these factors mediates the defects in axon guidance and neuronal survival observed in the sensory ganglia of Brn3a knockout mice.
Insights
Mice lacking Brn3a transcription factor show sensory neuron defects. This study found Bcl-2 and TAG-1 are unlikely to be regulated by Brn3a, suggesting other mechanisms for these developmental issues.
Area of Science:
- Developmental Neuroscience
- Molecular Biology
- Genetics
Background:
- Brn3a (POU-domain transcription factor) is crucial for sensory neuron development.
- Mice lacking Brn3a display trigeminal axon growth defects, sensory cell death, and perinatal mortality.
- Bcl-2 (apoptosis mediator) and TAG-1 (axon guidance molecule) have been proposed as Brn3a targets influencing sensory neuron survival and guidance.
Purpose of the Study:
- To investigate whether Bcl-2 and TAG-1 expression and function are altered in Brn3a knockout mice.
- To determine if Bcl-2 is a direct regulatory target of Brn3a.
- To assess the role of Bcl-2 and TAG-1 in the sensory axon guidance and neuronal survival defects observed in Brn3a knockout mice.
Main Methods:
- Harvesting trigeminal ganglia from embryonic day 13.5 wild-type and Brn3a knockout mouse embryos.
- Quantifying Bcl-2 and TAG-1 mRNA expression using reverse transcription polymerase chain reaction (RT-PCR).
- Examining TAG-1 expression in trigeminal and dorsal root ganglia via immunohistochemistry.
Main Results:
- Brn3a knockout mouse trigeminal ganglia showed comparable levels of Bcl-2 and TAG-1 mRNA to wild-type.
- Immunohistochemical analysis revealed similar TAG-1 staining in the sensory axons of both wild-type and Brn3a knockout embryos.
- No significant differences in Bcl-2 or TAG-1 expression were detected between genotypes.
Conclusions:
- Bcl-2 is unlikely to be a direct regulatory target of Brn3a.
- The observed defects in sensory axon guidance and neuronal survival in Brn3a knockout mice are probably not mediated by Bcl-2 or TAG-1.
- Further research is needed to identify the specific molecular pathways affected by Brn3a deficiency.
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