A huge thanks to all our colleagues for their feedback and support throughout this journey! 🥂✨

#DevelopmentalBiology #Neuroscience #SpinalCord #StemCells #ScienceAdvances

Our study demonstrates that temporal transcription factor expression across distinct cardinal domains specifies neuronal subtype identities.
➡️These findings provide evidence that spinal neuron diversity is generated through the integration of shared spatial and temporal patterning programs.

In the AS, the OPP sequence marks birth order: OC2 (early-deep), Pou2f2 (superficial), and Pou3f1 (late-deep). Pou2f2 loss reduces superficial Phox2a+ neurons and increases deep AS neurons and Pou2f2/Pou3f1 double+ cells, indicating re-specification to a later-born fate.

MN columnar identities follow the OPP sequence: OC2 (LMCm), Pou2f2 (LMCl), and Pou3f1 (MMC). Pou2f2 null mutants exhibit reduced LMCl neurons, while Pou3f1 loss impairs MMC development, proving the role of these TFs in chronological column specification.

EdU/BrdU birth-dating experiments confirm that this TF sequence correlates with the timing of neuronal birth. OC2 and Pou2f2 expression characterizes early-born populations, while Pou3f1 is expressed in neurons born at later stages.

We’ve identified a conserved temporal program driven by three transcription factors: OC2 > Pou2f2 > Pou3f1 ➡️OPP sequence — expressed across multiple cardinal domains, including motor neurons and anterolateral system (AS).

Our questions: Do spatial and temporal TF combinations specify molecularly and functionally defined neuronal subtypes? Are temporal TFs required for spinal projection neuron subtype specification?

⌛Here, we show that spatial patterning isn't the only factor— timing matters.

Happy to share that our work with Kevin Sangster and Artur Kania, is finally out! @sagnera.bsky.social We investigated the mechanisms that drive the chronological diversification of spinal neuron subtypes within cardinal classes. 🧵👇

Read it here: www.science.org/doi/10.1126/...