In vitro generation of Neuromesodermal Progenitor Cells

 

During normal embryonic development part of the posterior spinal cord, muscles and bones are generated from a neuromesodermal progenitor population (NMP) located in the caudal lateral epiblast region (CLE) of the embryo. FGF and Wnt signalling emanating from the posterior part of the embryo are instrumental fro the induction and maintenance of NMP cells. Following the cues from mouse embryonic development, we have recently described the in vitro generation of NMPs from mouse and human embryonic stem cells (ESCs) (Gouti et al,2014). These cells are characterized by the co-expression of the mesodermal marker Brachyury and the neural progenitor marker Sox2 in vitro and in vivo (Figure 1). The advantage of the system is that these cells can then be coaxed into either spinal cord neurons and / or paraxial mesoderm cells by exposure to specific signals at the correct time windows.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure1: NMPs co-express the neural factor Sox2 and the mesodermal factor Brachyury in vitro after a pulse of Wnt/FGF and in vivo at 8.5dpc mouse embryo.

 

The in vitro generation of NMPs provides a unique opportunity to study:

  • the process of axial elongation using a human organoid model (Figure 2)

  • the human specific aspects of neuromuscular system development in a neuromuscular organoid model

 

  • the mechanisms that regulate the divergence of the posterior neural and mesodermal lineages in the human embryo

 

  • the molecular mechanisms underlying human neuromuscular diseases

Figure 2: Axial elongation in human organoids. Brightfield images of representative organoids at day2, 6 and 8 of development reveals the formation of an anterior posterior axis in 3D.

Selected Publications

 

In vitro generation of neuromesodermal progenitors reveals distinct roles for wnt signalling in the specification of spinal cord and paraxial mesoderm identity.

 

Gouti M, Tsakiridis A, Wymeersch FJ, Huang Y, Kleinjung J, Wilson V, Briscoe J.

PLoS Biol. 2014 Aug 26;12(8)

 

The route to spinal cord cell types: a tale of signals and switches.

 

Gouti M, Metzis V, Briscoe J.

Trends Genet. 2015 Jun;31(6):282-9