AbstractDevelopment of the cerebellum involves the coordinated proliferation, differentiation, maturation, and integration of cells from multiple neuronal and glial lineages. In rodent models, much of this occurs in the early postnatal period. However, our understanding of the molecular mechanisms that regulate this phase of cerebellar development remains incomplete. Here, we address the role of the transcription factor nuclear factor one X (NFIX), in postnatal development of the cerebellum. NFIX is expressed by progenitor cells within the external granular layer and by cerebellar granule neurons within the internal granule layer. Using NFIX−/− mice, we demonstrate that the development of cerebellar granule neurons and Purkinje cells within the postnatal cerebellum is delayed in the absence of this transcription factor. Furthermore, the differentiation of mature glia within the cerebellum, such as Bergmann glia, is also significantly delayed in the absence of NFIX. Collectively, the expression pattern of NFIX, coupled with the delays in the differentiation of multiple cell populations of the developing cerebellum in NFIX−/− mice, suggest a central role for NFIX in the regulation of cerebellar development, highlighting the importance of this gene for the maturation of this key structure. J. Comp. Neurol. 519:3532–3548, 2011. © 2011 Wiley‐Liss, Inc.