The Transcription Factor Sp8 Is Required for the Production of Parvalbumin-Expressing Interneurons in the Olfactory Bulb

Abstract

Interneurons in the olfactory bulb (OB) represent a heterogeneous population, which are first produced at embryonic stages and persisting into adulthood. Using the BrdU birthdating method combined with immunostaining for several different neuronal markers, we provide the integrated temporal patterns of distinct mouse OB interneuron production from embryonic day 14 to postnatal day 365. We show that although the majority of OB interneuron subtypes continue to be generated throughout life, most subtypes show a similar “bell-like” temporal production pattern with a peak around birth. Tyrosine hydroxylase and calretinin-expressing interneurons are produced at a relatively low rate in the adult OB, while parvalbumin-expressing (PV+) interneuron production is confined to later embryonic and early postnatal stages. We also show that Dlx5/6− expressing progenitors contribute to PV+ interneurons in the OB. Interestingly, all PV+ interneurons in the external plexiform layer (EPL) express the transcription factor Sp8. Genetic ablation of Sp8 by cre/loxP based recombination severely reduces the number of PV+ interneurons in the EPL of the OB. Our results suggest that Sp8 is required for the normal production of PV+ interneurons in the EPL of the OB. These data expand our understanding of the temporal and molecular regulation of OB interneuron neurogenesis.

Transcription factors COUP-TFI and COUP-TFII are required for the production of granule cells in the mouse olfactory bulb

“…Immunohistochemistry was performed on cryostat 12 μm or 30 μm sections according to previous studies (Li et al, 2011;Ma et al, 2013). Sections were briefly boiled in 10 mM sodium citrate ( pH 6.0) for COUP-TFI, COUP-TFII and Ascl1 antigen retrieval.…”

“…Neural stem cells (NSCs) in the SVZ also generate oligodendrocytes and astrocytes (Merkle et al, 2004;Menn et al, 2006;Xing et al, 2014). Notably, NSCs in the embryonic ventricular zone and adult SVZ of the lateral ventricle are remarkably heterogeneous in terms of their location, transcription factor expression and potential to generate different subtypes of OB interneurons (Merkle et al, 2007(Merkle et al, , 2014Young et al, 2007;BatistaBrito et al, 2008;Yang, 2008;Kriegstein and Alvarez-Buylla, 2009;Li et al, 2011).…”

Sp8 plays a supplementary role to Pax6 in establishing the pMN/p3 domain boundary in the spinal cord

“…Serial sections of 14-20 µm were then cut and collected on Fisher Colorfrost-Plus slides. Immunohistochemistry was performed as previously described (Li et al, 2011b). Primary antibodies (supplementary material Table S1) were incubated overnight.…”

Mechanisms of Neurogenesis in the Normal and Injured Adult Brain

“…Several studies using knockout mice suggest that transcriptional factors such as Pax6 and Sp8 are required for the genesis of distinct subtypes of olfactory interneurons. [76][77][78][79] On the other hand, extrinsic factors including olfactory input from olfactory sensory neurons and centrifugal inputs from higher brain centers are also important for the maturation of new neurons in the OB.…”