Position-dependent plasticity of distinct progenitor types in the primitive streak

Abstract

The rostrocaudal (head-to-tail) axis is supplied by populations of progenitors at the caudal end of the embryo. Despite recent advances characterising one of these populations, the neuromesodermal progenitors, their nature and relationship to other populations remains unclear. Here we show that neuromesodermal progenitors are a single Sox2lowTlow entity whose choice of neural or mesodermal fate is dictated by their position in the progenitor region. The choice of mesoderm fate is Wnt/β-catenin dependent. Wnt/β-catenin signalling is also required for a previously unrecognised phase of progenitor expansion during mid-trunk formation. Lateral/ventral mesoderm progenitors represent a distinct committed state that is unable to differentiate to neural fates, even upon overexpression of the neural transcription factor Sox2. They do not require Wnt/β-catenin signalling for mesoderm differentiation. This information aids the correct interpretation of in vivo genetic studies and the development of in vitro protocols for generating physiologically-relevant cell populations of clinical interest.DOI: http://dx.doi.org/10.7554/eLife.10042.001

Embryonic timing, axial stem cells, chromatin dynamics, and the Hox clock

“…Its posterior-most portion produces the lateral and paraxial mesoderm from mesoderm progenitors (MPs) (Lawson et al 1991;Kinder et al 1999), whereas the rostral-most aspect of the streak abutting the node (the node-streak border) contains stem cell-like progenitors for both the mesoderm and neurectoderm Wilson 2002, 2007). These latter bipotent progenitors, called neuromesodermal progenitors (NMPs), appear in the embryo at around embryonic day 7.5 (E7.5), just before the first somite is formed (Wymeersch et al 2016). They constitute a tightly regulated and likely changing population of self-renewing cells, feeding the elongating axis with new mesoderm and neurectoderm tissues.…”

Early molecular events during retinoic acid induced differentiation of neuromesodermal progenitors

“…forebrain/midbrain). NMPs are unique in that they co-express Sox2 and T (Brachyury) that drive the neuroectodermal lineage and the mesodermal lineage, respectively (Martin and Kimelman, 2012; Olivera-Martinez et al, 2012; Tsakiridis et al, 2014; Wymeersch et al, 2016), along with Nkx1-2 which is a marker of all caudal progenitors (Delfino-Machin et al, 2005; Tamashiro et al, 2012; Sasai et al, 2014). A positive-feedback FGF and WNT signaling loop maintains an undifferentiated state in caudal progenitors that promote body axis extension (Ciruna and Rossant, 2001; Aulehla et al, 2003; Dunty et al, 2008; Naiche et al, 2011; Martin and Kimelman, 2012; Olivera-Martinez et al, 2012; Jurberg et al, 2014; Cunningham et al, 2015b).…”

Making muscle: skeletal myogenesisin vivoandin vitro

“…One type corresponds to a resident cell population able to give rise to both paraxial mesoderm and neural tube derivatives, the so-called neuromesodermal progenitors, which co-express the genes T and Sox2 (Garriock et al, 2015;Takemoto et al, 2011;Tzouanacou et al, 2009). A second type of progenitor gives rise only to paraxial mesoderm, while a third type can give rise to both paraxial mesoderm and lateral plate derivatives (Iimura et al, 2007;Stern and Canning, 1990;Wymeersch et al, 2016), and a fourth type can give rise to paraxial mesoderm and notochord (Selleck and Stern, 1991).…”