The developmental hourglass model is applicable to the spinal cord based on single‐cell transcriptomes and non‐conserved cis‐regulatory elements

Abstract

The developmental hourglass model predicts that embryonic morphology is most conserved at the mid‐embryonic stage and diverges at the early and late stages. To date, this model has been verified by examining the anatomical features or gene expression profiles at the whole embryonic level. Here, by data mining approach utilizing multiple genomic and transcriptomic datasets from different species in combination, and by experimental validation, we demonstrate that the hourglass model is also applicable to a reduced element, the spinal cord. In the middle of spinal cord development, dorsoventrally arrayed neuronal progenitor domains are established, which are conserved among vertebrates. By comparing the publicly available single‐cell transcriptome datasets of mice and zebrafish, we found that ventral subpopulations of post‐mitotic spinal neurons display divergent molecular profiles. We also detected the non‐conservation of cis‐regulatory elements located around the progenitor fate determinants, indicating that the cis‐regulatory elements contributing to the progenitor specification are evolvable. These results demonstrate that, despite the conservation of the progenitor domains, the processes before and after the progenitor domain specification diverged. This study will be helpful to understand the molecular basis of the developmental hourglass model.

A global gene regulatory program and its region-specific regulator partition neurons into commissural and ipsilateral projection types

“…The requirement of both Lhx2/9 and Nhlh1/2 for Robo3 expression in dI1 neurons suggests that the two groups of TFs may cooperate to achieve Robo3 activation possibly via binding to their respective cis-regulatory regions on the Robo3 genomic locus. A recent study identified an enhancer element 20 kb upstream of the Robo3 transcriptional start site that is conserved across vertebrates ( 63 ). They showed that a reporter gene expression driven by this enhancer element in chick spinal cord overlap with Robo3 expression and also overlap with Lhx1 expression.…”

Spinal cords: Symphonies of interneurons across species

“…Molecular studies will be important for understanding the relationship between gene expression and these divergent functions. Toward this end, recent studies have shown that V3 neurons in mice and zebrafish are molecularly heterogeneous ( Mukaigasa et al, 2021 ). This raises the possibility that these molecular subdivisions may, in mice, delineate the known anatomical and functional differences between subpopulations and, in zebrafish, define diverse, as of yet unknown, subpopulations for movement pattern generation.…”