Foxp- and Skor-family proteins control differentiation of Purkinje cells from Ptf1a and Neurogenin1-expressing progenitors in zebrafish

Abstract

Cerebellar neurons such as Purkinje cells (PCs) and granule cells (GCs) are differentiated from neural progenitors expressing proneural genes. Zebrafish mutants of proneural genesptf1aandneurogenin1showed a reduction or loss of PCs, GABAergic interneurons (INs), and reduced expression of GC progenitor genesatoh1a/b/c. Lineage tracing revealed that theptf1a-expressing progenitors gave rise to PCs, INs, and a part of GCs in zebrafish. These data indicate that theptf1a/neurognin1-expressing neural progenitors can generate a variety of cerebellar neurons. In this study, we found that genes encoding transcriptional regulators Foxp1b and Foxp4, as well as Skor1b and Skor2, which are reportedly expressed in PCs, were not expressed inptf1a;neurogenin1 mutants.foxp1b;foxp4mutants showed a strong reduction in PCs, whileskor1b;skor2mutants completely lacked PCs but instead displayed an increase in immature GCs. Misexpression ofskor2in GC progenitors expressingatoh1csuppressed GC fate. These data indicate that Foxp1b/4 and Skor1b/2 function as key transcriptional regulators in the initial step of PC differentiation fromptf1a/neurogenin1-expressing neural progenitors, while Skor1b and Skor2 control PC differentiation by suppressing their differentiation into GCs.