FBS Colloquia No.370Developmental Neurobiology Group

Role of the LIM-Homeodomain Transcription Factors in Axon Guidance of Purkinje Cells during Cerebellar Development

Purkinje cells (PCs), the sole output from the cerebellar cortex, are central to cerebellar processing for motor control and higher cognitive functions. Anatomically, their axons project to deep cerebellar nuclei and lateral vestibular nuclei as synapse-forming targets. To date, the dendritic development of PCs, which occurs postnatally in mice, has been extensively studied at cellular and molecular levels. However, the process of axon pathfinding by PCs, which occurs during embryonic development, remains poorly characterized. To address this issue, we analyzed in detail the behaviors of PC axons in embryonic mice, using the Ngn2 enhancer-based genetic approach that enables selective and sparse labeling of individual PCs from the outset of their axon growth. To unveil genetic programs for PC axon guidance, we next examined the role of transcription factors uniquely expressed in PCs by loss-of-function strategies in vivo. In this study, we focused our attention on the role of the LIM-homeodomain (LIM-HD) transcription factors Lhx1 and Lhx5, since these LIM-HD transcription factors start to be expressed in PCs when PCs initiate axon growth and continue to be expressed during PC axon pathfinding toward their targets. Our results suggest that Lhx1 and Lhx5 confers developing PC axons with specific navigational properties during their growth toward their targets.