Abstract

To ensure the formation of a properly patterned embryo, multiple processes must operate harmoniously at sequential phases of development. This is implemented by mutual interactions between cells and tissues that together regulate the segregation and specification of cells, their growth and morphogenesis. The formation of the spinal cord and paraxial mesoderm derivatives exquisitely illustrate these processes. Following early gastrulation, while the vertebrate body elongates, a population of bipotent neuromesodermal progenitors resident in the posterior region of the embryo generate both neural and mesodermal lineages. At later stages, the somitic mesoderm regulates aspects of neural patterning and differentiation of both central and peripheral neural progenitors. Reciprocally, neural precursors influence the paraxial mesoderm to regulate somite-derived myogenesis and additional processes by distinct mechanisms. Central to this crosstalk is the activity of the axial notochord, which, via sonic hedgehog signaling, plays pivotal roles in neural, skeletal muscle and cartilage ontogeny. Here, we discuss the cellular and molecular basis underlying this complex developmental plan, with a focus on the logic of sonic hedgehog activities in the coordination of the neural-mesodermal axis.

Highlights

  • Growing evidence substantiates the significance of interactions between the above neuromesodermal progenitors (NMPs) derivatives; from neural tube (NT) patterning and differentiation of specific cell types to induction of neural crest (NC) cells, control of NC emigration and migration followed by peripheral nervous system segmentation, all of which are modulated by mesodermal signals

  • The complex events leading from NMPs to paraxial mesoderm and NT, and ensuing interactions leading to coordinated formation of their respective derivatives, embody most of the basic processes in embryogenesis, from cell fate decisions to cell proliferation, migration, terminal differentiation and patterned morphogenesis

  • Much is still to be uncovered regarding the relationship between cell fate acquisition and morphogenesis, by addressing dynamic processes such as epithelial-to-mesenchymal transition (EMT) and cell migration

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Summary

Introduction

NMPs are located in a caudal embryonic structure, the tailbud, and represent a common pool of bipotent progenitors able to generate caudal spinal cord neurectoderm and paraxial mesoderm tissues [1,2] As such, they are identified by the coexpression of transcription factors that characterize gastrulation, mesoderm, and neural development such as T(Brachyury), Sox and Nkx1/2 [3,4]. Labeling was encountered in cells that express neural plate border and early NC genes and in neuronal trunk derivatives such as dorsal root ganglia [8] Together, these results suggest that at least some trunk-level NC progenitors derive from NMPs. Here, we briefly and separately introduce the three interacting players in trunk patterning and morphogenesis: the paraxial mesoderm, the NT and the NC. In the forthcoming sections, we elaborate on the molecular nature of interactions between these components and on their developmental outcomes

Paraxial Mesoderm
Neural Tube
The Neural Crest
Factors Underlying the Choice of NMPs to Generate Neural or Mesodermal Fates
The Timing of NC EMT
Segmental Migration of NC and Patterning of the PNS
Melanoblast Migration along the Dermomyotome-Derived Dermis
NC-Mesoderm Interactions in the Regulation of Myogenesis
Shh in Muscle Development
Shh and Cartilage Development
Shh in the Coordination of Neural-Mesodermal Development
Conclusions and Future Perspectives
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