AUTHOR=Hagan Nellwyn , Guarente Juliana , Ellisor Debra , Zervas Mark 

TITLE=The Temporal Contribution of the Gbx2 Lineage to Cerebellar Neurons

JOURNAL=Frontiers in Neuroanatomy

VOLUME=11

YEAR=2017

URL=https://www.frontiersin.org/journals/neuroanatomy/articles/10.3389/fnana.2017.00050

DOI=10.3389/fnana.2017.00050

ISSN=1662-5129

ABSTRACT=<p>The cerebellum (Cb) is an exquisite structure that controls elaborate motor behaviors and is essential for sensory-motor learning. During development, the Cb is derived from rhombomere 1 (r1). Within this embryonic compartment, precursors in r1 are patterned by signaling cues originating from the <underline>is</underline>thmus <underline>o</underline>rganizer (IsO) and subsequently undergo complex morphogenic movements to establish their final position in the mature Cb. The transcription factor <italic>Gbx2</italic> is expressed in the developing Cb and is intimately involved in organizing and patterning the Cb. Nevertheless, how precursors expressing <italic>Gbx2</italic> at specific embryonic time points contribute to distinct cell types in the adult Cb is unresolved. In this study, we used <underline>G</underline>enetic <underline>I</underline>nducible <underline>F</underline>ate <underline>M</underline>apping (GIFM) to mark <italic>Gbx2</italic>-expressing precursors with fine temporal resolution and to subsequently track this lineage through embryogenesis. We then determined the terminal neuronal fate of the <italic>Gbx2</italic> lineage in the adult Cb. Our analysis demonstrates that the <italic>Gbx2</italic> lineage contributes to the Cb with marking over the course of five stages: Embryonic day 7.5 (E7.5) through E11.5. The <italic>Gbx2</italic> lineage gives rise to Purkinje cells, granule neurons, and deep cerebellar neurons across these marking stages. Notably, the contribution of the <italic>Gbx2</italic> lineage shifts as development proceeds with each marking stage producing a distinct profile of mature neurons in the adult Cb. These findings demonstrate the relationship between the temporal expression of <italic>Gbx2</italic> and the terminal cell fate of neurons in the Cb. Based on these results, <italic>Gbx2</italic> is critical to Cb development, not only for its well-defined role in positioning and maintaining the IsO, but also for guiding the development of Cb precursors and determining the identity of Cb neurons.</p>