Posterior enhancer (p-Enh) maintains early neuromesodermal progenitors bi-potency during gastrulation

Area of Science:

• Developmental Biology
• Genetics
• Molecular Biology

Background:

• Vertebrate axis patterning relies on neuromesodermal progenitors (NMPs) for spinal cord (SC) and presomitic mesoderm (PSM) development.
• A previously identified posterior enhancer (p-Enh) is vital for posterior tissue formation but its role in early NMPs was unknown.

Purpose of the Study:

• To investigate the role of the p-Enh in regulating NMP differentiation and composition.
• To understand how p-Enh influences early embryonic development and posterior patterning.

Main Methods:

• Utilized an in vitro NMP differentiation system.
• Performed time-resolved transcriptomic analysis and experimental characterization.
• Developed and applied a bioinformatic tool (ST-Pheno) to link in vitro and in vivo data.

Main Results:

• Genetic removal of p-Enh caused aberrant upregulation of PSM genes during differentiation.
• Disorganized NMP composition, specifically an over-representation of T^highSOX2^low NMPs, was observed.
• ST-Pheno analysis revealed T^highSOX2^low NMPs enrichment in specific embryonic regions, potentially disrupting SC and PSM development.

Conclusions:

• p-Enh plays a critical role in controlling NMP subtype composition during mammalian embryogenesis.
• This finding enhances the molecular understanding of vertebrate axis patterning and posterior development.