Collapse of embryonic identities and emergence of functional diversity during motor neuron maturation

However, this extensive transcriptional diversity is largely lost as gene expression programs that define column and pool identities are downregulated during perinatal and early postnatal life. The loss of embryonic diversity is accompanied by the gradual gain of gene expression programs that define morphologically and functionally distinct alpha, gamma, and type3 identities, which are then maintained into adulthood. The changes in SMN diversity are accompanied by changes in accessible chromatin regions and transcription factor (TF) enrichment.

Differential ATAC-seq peaks and TFs that define embryonic diversity are lost over time while new peaks and TF-motifs that drive expression in adult subtypes are gained. Our work uncovers a novel maturation trajectory for postmitotic neurons where extensive spatial diversity is first acquired in the embryo to ensure proper circuit wiring; this diversity is then lost as maturing neurons re-diversify into functional identities required for proper circuit firing in postnatal life.

Therefore, all aspects of a neuron’s identity - its morphology, circuitry, and electrophysiologically - may not be fully described by its gene expression program at adulthood, but instead is a culmination of transcriptional events that occur throughout its specification and maturation trajectory.