Lineage tracing of neuromesodermal progenitors reveals novel Wnt-dependent roles in trunk progenitor cell maintenance and differentiation.
In the development of the vertebrate body plan, Wnt3a is thought to promote the formation of paraxial mesodermal progenitors (PMPs) of the trunk region while suppressing neural specification. Recent lineage-tracing experiments have demonstrated that these trunk neural progenitors and PMPs derive from a common multipotent progenitor called the neuromesodermal progenitor (NMP). NMPs are known to reside in the anterior primitive streak (PS) region; however, the extent to which NMPs populate the PS and contribute to the vertebrate body plan, and the precise role that Wnt3a plays in regulating NMP self-renewal and differentiation are unclear. To address this, we used cell-specific markers (Sox2 and T) and tamoxifen-induced Cre recombinase-based lineage tracing to locate putative NMPs in vivo. We provide functional evidence for NMP location primarily in the epithelial PS, and to a lesser degree in the ingressed PS. Lineage-tracing studies in Wnt3a/β-catenin signaling pathway mutants provide genetic evidence that trunk progenitors normally fated to enter the mesodermal germ layer can be redirected towards the neural lineage. These data, combined with previous PS lineage-tracing studies, support a model that epithelial anterior PS cells are Sox2(+)T(+) multipotent NMPs and form the bulk of neural progenitors and PMPs of the posterior trunk region. Finally, we find that Wnt3a/β-catenin signaling directs trunk progenitors towards PMP fates; however, our data also suggest that Wnt3a positively supports a progenitor state for both mesodermal and neural progenitors.
Center for Cancer Research, Cancer and Developmental Biology Laboratory, Cell Signaling in Vertebrate Development Section, NCI-Frederick, NIH, Frederick, MD 21702, USA.
Robert J
RJ
Garriock
Center for Cancer Research, Cancer and Developmental Biology Laboratory, Cell Signaling in Vertebrate Development Section, NCI-Frederick, NIH, Frederick, MD 21702, USA.
Ravindra B
RB
Chalamalasetty
Center for Cancer Research, Cancer and Developmental Biology Laboratory, Cell Signaling in Vertebrate Development Section, NCI-Frederick, NIH, Frederick, MD 21702, USA.
Mark W
MW
Kennedy
Center for Cancer Research, Cancer and Developmental Biology Laboratory, Cell Signaling in Vertebrate Development Section, NCI-Frederick, NIH, Frederick, MD 21702, USA.
Lauren C
LC
Canizales
Center for Cancer Research, Cancer and Developmental Biology Laboratory, Cell Signaling in Vertebrate Development Section, NCI-Frederick, NIH, Frederick, MD 21702, USA.
Mark
M
Lewandoski
Center for Cancer Research, Cancer and Developmental Biology Laboratory, Cell Signaling in Vertebrate Development Section, NCI-Frederick, NIH, Frederick, MD 21702, USA yamagute@mail.nih.gov.
Terry P
TP
Yamaguchi
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D006652:Histological Techniques; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008648:Mesoderm / Q000166:cytology / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D058953:Neural Stem Cells / Q000502:physiology*; D054240:Primitive Streak / Q000166:cytology*; D015398:Signal Transduction / Q000502:physiology*; D060509:Wnt3A Protein / Q000378:metabolism
D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse
Brachyury; Neural progenitor; Neuromesodermal progenitor; Paraxial mesoderm; Sox2; Wnt signaling