A dual role for the transcription factor Sp8 in postnatal neurogenesis

Neural stem cells (NSCs) of the postnatal subventricular zone (SVZ) continue producing distinct subtypes of olfactory bulb (OB) interneurons throughout life. Understanding the transcriptional coding of this diversity remains a great challenge of modern neurosciences. Interneurons expressing calretinin (CalR) represent the main interneuron subtype produced in the glomerular cell layer (GL) after birth. Previous studies have suggested that their specification relies on expression of the transcription factor Sp8 by SVZ NSCs. In this study, we performed fate mapping of NSCs that generate CalR+ or non-CalR+ interneurons, in order to assess the pattern of Sp8 expression during postnatal neurogenesis. We highlight a complex pattern of Sp8 expression, which appears to be expressed in all interneurons lineages, before getting gradually restricted to maturing CalR+ interneurons. To decipher the early and late functions of Sp8 in postnatal OB neurogenesis, we combined transient, permanent and conditional genetic approaches to manipulate Sp8 at distinct neurogenic stages. While Sp8 plays an early role in controlling proliferation in all lineages, it is not involved in the early specification of CalR+ periglomerular interneurons, but plays a crucial role in their long term survival. Together, our results highlight a crucial and dual role for Sp8 during postnatal neurogenesis.