TY - JOUR
T1 - Npas4 regulates Mdm2 and thus Dcx in experience-dependent dendritic spine development of newborn olfactory bulb interneurons
AU - Yoshihara, Sei Ichi
AU - Takahashi, Hiroo
AU - Nishimura, Nobushiro
AU - Kinoshita, Masahito
AU - Asahina, Ryo
AU - Kitsuki, Michiko
AU - Tatsumi, Kana
AU - Furukawa-Hibi, Yoko
AU - Hirai, Hirokazu
AU - Nagai, Taku
AU - Yamada, Kiyofumi
AU - Tsuboi, Akio
N1 - Funding Information:
This work was supported by Grants-in-Aid for Scientific Research for (B) (A.T.) and (C) (H.T. and S.Y.) and Challenging Exploratory Research (A.T.) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. A.T. was supported by grants from the SKYLARK Food Science Institute, Uehara Memorial, Smoking Research, Asahi Research Promotion, and Yamada Science Foundations, Japan. S.Y. and H.T. were supported by grants from Takeda Science Foundation and Astellas Foundation for Research on Metabolic Disorders, Japan. H.T. was supported by a grant from the Salt Science Research Foundation (no. 14C3), Japan. We gratefully thank M. E. Greenberg for the generous gift of the Npas4 mutant mice and the animal facility staff of Nara Medical University and Nagoya University for their expert assistance.
PY - 2014/8/7
Y1 - 2014/8/7
N2 - 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.
AB - 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.
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U2 - 10.1016/j.celrep.2014.06.056
DO - 10.1016/j.celrep.2014.06.056
M3 - Article
C2 - 25088421
AN - SCOPUS:84924631391
VL - 8
SP - 843
EP - 857
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 3
ER -