Npas4 regulates Mdm2 and thus Dcx in experience-dependent dendritic spine development of newborn olfactory bulb interneurons

Sei Ichi Yoshihara, Hiroo Takahashi, Nobushiro Nishimura, Masahito Kinoshita, Ryo Asahina, Michiko Kitsuki, Kana Tatsumi, Yoko Furukawa-Hibi, Hirokazu Hirai, Taku Nagai, Kiyofumi Yamada, Akio Tsuboi

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Sensory experience regulates the development of various brain structures, including the cortex, hippocampus, and olfactory bulb (OB). Little is known about how sensory experience regulates the dendritic spine development of OB interneurons, such as granule cells (GCs), although it is well studied in mitral/tufted cells. Here, we identify a transcription factor, Npas4, which is expressed in OB GCs immediately after sensory input and is required for dendritic spine formation. Npas4 overexpression in OB GCs increases dendritic spine density, even under sensory deprivation, and rescues reduction of dendrite spine density in the Npas4 knockout OB. Furthermore, loss of Npas4 upregulates expression of the E3-ubiquitin ligase Mdm2, which ubiquitinates a microtubule-associated protein Dcx. This leads to reduction in the dendritic spine density of OB GCs. Together, these findings suggest that Npas4 regulates Mdm2 expression to ubiquitinate and degrade Dcx during dendritic spine development in newborn OB GCs after sensory experience.

Original languageEnglish
Pages (from-to)843-857
Number of pages15
JournalCell Reports
Volume8
Issue number3
DOIs
Publication statusPublished - 07-08-2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Npas4 regulates Mdm2 and thus Dcx in experience-dependent dendritic spine development of newborn olfactory bulb interneurons'. Together they form a unique fingerprint.

Cite this