Semaphorin-3A (Sema3A) is an attractive guidance molecule for cortical
apical dendrites. To elucidate the role of Sema3A in
hippocampal dendritic formation, we examined the Sema3A expression pattern in the perinatal
hippocampal formation and analyzed
hippocampal dendrites of
the brains from young adult sema3A
mutant mice. Sema3A protein was predominantly expressed in the
hippocampal plate and the inner
marginal zone at the initial period of apical
dendritic growth.
Neuropilin-1 and plexin-A, the receptor components for Sema3A, were also localized in the same regions. The Golgi
impregnation method revealed that in
wildtype mice more than 90% of
hippocampal CA1 pyramidal neurons extended a single trunk or apical trunks bifurcated in stratum radiatum. Seven percent of the
pyramidal neurons showed
proximal bifurcation of apical trunks in stratum pyramidale or at the border of the stratum pyramidale and stratum radiatum. In sema3A
mutant mice,
proximally bifurcated
apical dendrites were increased to 32%, while the single apical
dendritic pyramidal neurons were decreased. We designate this
phenotype in sema3A
mutant mice as "
proximal bifurcation." In the dissociated culture system, approximately half of the
hippocampal neurons from
wildtype mice resembled
pyramidal neurons, which possess a long, thick, and tapered
dendrite. In contrast, only 30% of the
neurons from sema3A
mutants exhibited pyramidal-like morphology.
Proximal bifurcation of
CA1 pyramidal neurons was also increased in the
mutant mice of p35, an activator of
cyclin-dependent kinase 5 (Cdk5). Thus, Sema3A may facilitate the initial growth of
CA1 apical dendrites via the
activation of p35/Cdk5, which may in turn signal
hippocampal development.
