PT  - JOURNAL ARTICLE
AU  - Anders Lunde
AU  - Benjamin W. Okaty
AU  - Susan M. Dymecki
AU  - Joel C. Glover
TI  - Molecular profiling defines evolutionarily conserved transcription factor signatures of major vestibulospinal neuron groups
AID  - 10.1523/ENEURO.0475-18.2019
DP  - 2019 Feb 01
TA  - eneuro
PG  - ENEURO.0475-18.2019
4099  - http://www.eneuro.org/content/early/2019/02/01/ENEURO.0475-18.2019.short
4100  - http://www.eneuro.org/content/early/2019/02/01/ENEURO.0475-18.2019.full
AB  - Vestibulospinal neurons are organized into discrete groups projecting from brainstem to spinal cord, enabling vertebrates to maintain proper balance and posture. The two largest groups are the lateral vestibulospinal tract (LVST) group and the contralateral medial vestibulospinal tract (cMVST) group, with different projection lateralities and functional roles. In search of a molecular basis for these differences, we performed RNA sequencing on LVST and cMVST neurons from mouse and chicken embryos followed by immunohistofluorescence validation. Focusing on transcription factor (TF)-encoding genes, we identified TF signatures that uniquely distinguish the LVST from the cMVST group and further parse different rhombomere-derived portions comprising the cMVST. Immunohistofluorescence assessment of the CNS from spinal cord to cortex demonstrated that these TF signatures are restricted to the respective vestibulospinal groups and some neurons in their immediate vicinity. Collectively, these results link the combinatorial expression of TFs to developmental and functional subdivisions within the vestibulospinal system.Significance statement: The molecular underpinnings of hodological and functional subdivisions within brainstem-to-spinal cord projection neurons are poorly understood. Transcriptomic profiling is an important step towards obtaining a molecular characterization of individual projection neuron groups and identifying candidate genes potentially involved in their specification. Here we use this approach to identify transcription factor signatures conserved in mouse and chicken that distinguish the two major vestibulospinal projection neuron groups and define coherent subpopulations within them, using whole transcriptome sequencing and immunohistofluorescence combined with retrograde tracing.