The Cerebellum

, Volume 11, Issue 1, pp 41-49

First online:

Nuclear Factor I and Cerebellar Granule Neuron Development: An Intrinsic–Extrinsic Interplay

  • Daniel L. KilpatrickAffiliated withDepartment of Microbiology and Physiological Systems, and Program in Neuroscience, University of Massachusetts Medical School Email author 
  • , Wei WangAffiliated withStem Cell & Regenerative Medicine International
  • , Richard GronostajskiAffiliated withDepartment of Biochemistry and Program in Neuroscience, State University of New York
  • , E. David LitwackAffiliated withDepartment of Anatomy and Neurobiology and Program in Neuroscience, Baltimore, School of Medicine, University of Maryland

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Granule neurons have a central role in cerebellar function via their synaptic interactions with other neuronal cell types both within and outside this structure. Establishment of these synaptic connections and its control is therefore essential to their function. Both intrinsic as well as environmental mechanisms are required for neuronal development and formation of neuronal circuits, and a key but poorly understood question is how these various events are coordinated and integrated in maturing neurons. In this review, we summarize recent work on the role of the Nuclear Factor I family in the transcriptional programming of cerebellar granule neuron maturation and synapse formation. In particular, we describe (1) the involvement of this family of factors in key developmental steps occurring throughout postmitotic granule neuron development, including dendrite and synapse formation and synaptic receptor expression, and (2) the mediation of these actions by critical downstream gene targets that control cell–cell interactions. These findings illustrate how Nuclear Factor I proteins and their regulons function as a “bridge” between cell-intrinsic and cell-extrinsic interactions to control multiple phases of granule neuron development.


Neuronal differentiation Transcription factor Axonogenesis Migration Dendritogenesis Synaptogenesis