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

Area of Science:

• Neuroscience
• Developmental Biology

Background:

• Neural stem cells in the postnatal ventricular-subventricular zone (V-SVZ) generate interneurons that migrate to the olfactory bulb (OB).
• Transcription factors Sp8 and Sp9 are present in the V-SVZ-rostral migratory stream-OB system.

Purpose of the Study:

• To investigate the coordinated role of Sp8 and Sp9 transcription factors in olfactory bulb interneuron development.

Main Methods:

• Conditional gene deletion of Sp8 and Sp9 in mice.
• RNA sequencing (RNA-Seq) and RNA in situ hybridization.
• Analysis of OB interneuron number, differentiation, migration, and cell death.

Main Results:

• Conditional deletion of both Sp8 and Sp9 caused a severe reduction in OB interneuron number.
• Double mutants exhibited defects in neuronal differentiation, migration, and increased cell death.
• Sp8/Sp9 double mutants failed to express Prokr2 and Tshz1 in neuroblasts, unlike single mutants.

Conclusions:

• Sp8 and Sp9 transcription factors coordinately regulate OB interneuron development.
• The loss of Sp8 and Sp9 function disrupts neuroblast expression of Prokr2 and Tshz1, impacting interneuron development and migration.
• These findings highlight the critical role of Sp8/Sp9 in the V-SVZ-RMS-OB system and link to human Kallmann syndrome.