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Updated: May 25, 2026
Horizontal Hippocampal Slices of the Mouse Brain
Published on: September 22, 2020
CRMP4 suppresses apical dendrite bifurcation of CA1 pyramidal neurons in the mouse hippocampus
Emi Niisato1, Jun Nagai, Naoya Yamashita
1Department of Life Science and Medical Bioscience, Waseda University, Tokyo 162-8480, Japan.
Abstract:
Collapsin response mediator proteins (CRMPs) are a family of cytosolic phosphoproteins that consist of 5 members (CRMP 1-5). CRMP2 and CRMP4 regulate neurite outgrowth by binding to tubulin heterodimers, resulting in the assembly of microtubules. CRMP2 also mediates the growth cone collapse response to the repulsive guidance molecule semaphorin-3A (Sema3A). However, the role of CRMP4 in Sema3A signaling and its function in the developing mouse brain remain unclear. We generated CRMP4-/- mice in order to study the in vivo function of CRMP4 and identified a phenotype of proximal bifurcation of apical dendrites in the CA1 pyramidal neurons of CRMP4-/- mice. We also observed increased dendritic branching in cultured CRMP4-/- hippocampal neurons as well as in cultured cortical neurons treated with CRMP4 shRNA. Sema3A induces extension and branching of the dendrites of hippocampal neurons; however, these inductions were compromised in the CRMP4-/- hippocampal neurons. These results suggest that CRMP4 suppresses apical dendrite bifurcation of CA1 pyramidal neurons in the mouse hippocampus and that this is partly dependent on Sema3A signaling.
Insights
Collapsin response mediator protein 4 (CRMP4) suppresses apical dendrite bifurcation in mouse hippocampal neurons. Its absence leads to increased branching, partly mediated by semaphorin-3A signaling.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Collapsin response mediator proteins (CRMPs) are key regulators of neuronal development.
- CRMP2 and CRMP4 are known to influence neurite outgrowth and microtubule assembly.
- The specific role of CRMP4 in semaphorin-3A (Sema3A) signaling and brain development is not well understood.
Purpose of the Study:
- To investigate the in vivo function of CRMP4 in the developing mouse brain.
- To elucidate the role of CRMP4 in Sema3A signaling pathways.
- To determine CRMP4's contribution to neuronal morphology, specifically dendritic branching.
Main Methods:
- Generation and analysis of CRMP4 knockout (CRMP4-/-) mice.
- Histological examination of CA1 pyramidal neurons in the hippocampus.
- In vitro studies using cultured hippocampal and cortical neurons with CRMP4 knockdown (shRNA).
- Assessment of dendritic branching and extension in response to Sema3A.
Main Results:
- CRMP4-/- mice exhibit proximal apical dendrite bifurcation in CA1 pyramidal neurons.
- CRMP4 deficiency leads to increased dendritic branching in cultured hippocampal and cortical neurons.
- Sema3A-induced dendritic extension and branching are impaired in CRMP4-/- hippocampal neurons.
Conclusions:
- CRMP4 acts as a suppressor of apical dendrite bifurcation in CA1 pyramidal neurons.
- This suppressive function is, in part, dependent on Sema3A signaling.
- CRMP4 plays a crucial role in regulating hippocampal neuronal architecture during development.
