The PROK2/PROKR2 signaling pathway is required for the migration of most olfactory bulb interneurons.

Neural stem cells in the subventricular zone (SVZ) of the lateral ventricle generate new interneurons, which migrate tangentially through the rostral migratory stream (RMS) to the olfactory bulb (OB). The PROK2 (prokineticin 2) and PROKR2 (prokineticin receptor 2) signaling pathway has been identified to cause human Kallmann syndrome, a developmental disease that associates hypogonadism with anosmia (OB developmental defects). However, the identities and properties of PROK2 and PROKR2 cells in the SVZ-RMS-OB remain largely unknown.

Transcription factors Sp8 and Sp9 regulate the development of caudal ganglionic eminence-derived cortical interneurons.

Cortical interneurons are derived from the subcortical medial ganglionic eminence (MGE), caudal ganglionic eminence (CGE) and preoptic area (POA). CGE-derived cortical interneurons, which comprise around 30% of all cortical interneurons, mainly express Htr3a, calretinin (CR), Reelin (RELN) and vasoactive intestinal polypeptide (VIP). In the present study, we show that transcription factors Sp8 and Sp9 are co-expressed in the subventricular zone (SVZ) of the dorsal CGE.

Transcription Factors and Regulate Medial Ganglionic Eminence-Derived Cortical Interneuron Migration.

Cortical interneurons are derived from the subpallium and reach the developing cortex through long tangential migration. Mature cortical interneurons are characterized by remarkable morphological, molecular, and functional diversity. The calcium-binding protein parvalbumin (PV) and neuropeptide somatostatin (SST) identify most medial ganglionic eminence (MGE)-derived cortical interneurons.

Dlx1/2 are Central and Essential Components in the Transcriptional Code for Generating Olfactory Bulb Interneurons.

Generation of olfactory bulb (OB) interneurons requires neural stem/progenitor cell specification, proliferation, differentiation, and young interneuron migration and maturation. Here, we show that the homeobox transcription factors Dlx1/2 are central and essential components in the transcriptional code for generating OB interneurons. In Dlx1/2 constitutive null mutants, the differentiation of GSX2+ and ASCL1+ neural stem/progenitor cells in the dorsal lateral ganglionic eminence is blocked, resulting in a failure of OB interneuron generation.

Sp9 Regulates Medial Ganglionic Eminence-Derived Cortical Interneuron Development.

Immature neurons generated by the subpallial MGE tangentially migrate to the cortex where they become parvalbumin-expressing (PV+) and somatostatin (SST+) interneurons. Here, we show that the Sp9 transcription factor controls the development of MGE-derived cortical interneurons. SP9 is expressed in the MGE subventricular zone and in MGE-derived migrating interneurons.

Transcription Factors Sp8 and Sp9 Coordinately Regulate Olfactory Bulb Interneuron Development.

Neural stem cells in the postnatal telencephalic ventricular-subventricular zone (V-SVZ) generate new interneurons, which migrate tangentially through the rostral migratory stream (RMS) into the olfactory bulb (OB). The Sp8 and Sp9 transcription factors are expressed in neuroblasts, as well as in the immature and mature interneurons in the V-SVZ-RMS-OB system. Here we show that Sp8 and Sp9 coordinately regulate OB interneuron development: although Sp9 null mutants show no major OB interneuron defect, conditional deletion of both Sp8 and Sp9 resulted in a much more severe reduction of OB interneuron number than that observed in the Sp8 conditional mutant mice, due to defects in neuronal differentiation, tangential and radial migration, and increased cell death in the V-SVZ-RMS-OB system.