Neurogenin 3 cellular and subcellular localization in the developing and adult hippocampus

Abstract

Neurogenin 3 (Ngn3), a proneural gene controlled by the Notch receptor, is implicated in the control of dendrite morphology and synaptic plasticity of cultured hippocampal neurons. Here we report the localization and subcellular distribution of Ngn3 in the hippocampus in vivo and in neuronal cultures. In situ hybridization showed Ngn3 mRNA expression in the pyramidal layer and dentate gyrus of adult mouse hippocampus. Immunohistochemistry studies revealed that Ngn3 localization is mostly cytoplasmic in the hippocampal eminence at embryonic day (E)17 and postnatal day (P)0. At P10 it is cytoplasmic in CA1-CA3 pyramidal neurons and nuclear in granule cells of the dentate gyrus. In the adult hippocampus Ngn3 is localized in the nucleus and cytoplasm of both pyramidal neurons and granule cells. During development of cultured hippocampal neurons, Ngn3 mRNA expression is higher at stages of neuronal polarization, as judged by reverse-transcription polymerase chain reaction (RT-PCR), and it is mostly cytoplasmic. The tracking of the subcellular localization of Ngn3 in neurons infected with a virus expressing myc-Ngn3 suggests that the protein is quickly translocated to the cell nucleus after synthesis and then reexported to the cytoplasm. Treatment with leptomycin B, a potent and specific inhibitor of the exportin CRM1, induced its accumulation into the nucleus, suggesting that CRM1 mediates the nuclear export of Ngn3. These results suggest that Ngn3 may play a role in neuronal development by actions in the cytoplasm.

Oestradiol synthesized by female neurons generates sex differences in neuritogenesis

“…Previous studies on unsexed primary neuronal cultures from the foetal mouse hippocampus have shown that there is a transitory peak in the expression of the neuritogenic factor Ngn3 that is associated with the earlier phases of neuritogenesis1216. Our present findings indicate that the Ngn3 peak is advanced in female hippocampal neurons compared to males.…”

“…Previous studies in unsexed cultures have shown that Ngn3 is a neuritogenic factor in hippocampal neurons and that Ngn3 expression increases during neuronal differentiation in vitro and reaches a maximum during the early neuritogenic period12. Hence, we speculated that basal sex differences in neuritogenesis in male and female hippocampal neurons should be associated with sex differences in Ngn3 expression.…”

Molecular mechanisms involved in the regulation of neuritogenesis by estradiol: Recent advances

“…hippocampal neurons [49][50][51]. Recent studies have shown that estradiol inhibits Notch signaling in developing hippocampal neurons [52,53], increasing the expression of Ngn3 and the growth of dendrites [53].…”

Endocrine Pancreas Development and Regeneration: Noncanonical Ideas From Neural Stem Cell Biology

“…This would also raise the possibility that, being a bHLH factor, Hes3 may interfere with the actions of other bHLH factors of importance to pancreatic development and function such as Ngn3 (5,73,87,88). In another parallel between brain and pancreas, Ngn3 has important functions in the development of the brain (including hippocampal and hypothalamic neurons and glial progenitors), islet cell specification, and b-cell regeneration (18,(89)(90)(91).…”