Abstract
ABSTRACTThe vertebrate body forms by continuous generation of new tissue from progenitors at the posterior end of the embryo. The study of these axial progenitors has proved to be challenging in vivo largely because of the lack of unique molecular markers to identify them. Here, we elucidate the expression pattern of the transcription factor Nkx1-2 in the mouse embryo and show that it identifies axial progenitors throughout body axis elongation, including neuromesodermal progenitors and early neural and mesodermal progenitors. We create a tamoxifen-inducible Nkx1-2CreERT2 transgenic mouse and exploit the conditional nature of this line to uncover the lineage contributions of Nkx1-2-expressing cells at specific stages. We show that early Nkx1-2-expressing epiblast cells contribute to all three germ layers, mostly neuroectoderm and mesoderm, excluding notochord. Our data are consistent with the presence of some self-renewing axial progenitors that continue to generate neural and mesoderm tissues from the tail bud. This study identifies Nkx1-2-expressing cells as the source of most trunk and tail tissues in the mouse and provides a useful tool to genetically label and manipulate axial progenitors in vivo.
Highlights
The vertebrate body forms progressively in a head-to-tail direction from progenitors located at the posterior end of the embryo
Nkx1-2 is expressed in the posterior growth zone throughout body axis elongation To document in detail Nkx1-2 expression in the mouse embryo, we carried out whole-mount RNA in situ hybridisation and localised Nkx1-2 transcripts to specific cell populations in serial transverse sections
The expression pattern and relative levels of Nkx1-2 in the E8.5 embryo combined with lineagetracing data (Cambray and Wilson, 2007; Wymeersch et al, 2016) support single-cell transcriptomics data suggesting that Nkx1-2 is highly expressed in neuromesodermal progenitors (NMPs) and expressed at lower levels in early neural and mesodermal progenitors (Gouti et al, 2017; Koch et al, 2017)
Summary
The vertebrate body forms progressively in a head-to-tail direction from progenitors located at the posterior end of the embryo (reviewed by Kimelman, 2016; Neijts et al, 2013; Wilson et al, 2009). In agreement with a recent report (Javali et al, 2017), we found low but detectable levels of TBX6 protein in all SOX2+ cells in the CNH region, including Nkx1-2-expressing cells in the neural tube (higher in the ventral half ) and in the neuromesodermal lip (Fig. S2).
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