Lineage tracing of neuromesodermal progenitors reveals novel Wnt-dependent roles in trunk progenitor cell maintenance and differentiation

Garriock, Robert J.; Chalamalasetty, Ravindra B.; Kennedy, Mark W.; Canizales, Lauren C.; Lewandoski, Mark; Yamaguchi, Terry P.

doi:10.1242/dev.111922

Cited by 115 publications

(160 citation statements)

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“…Combined with results from PWPCs in zebrafish, mouse and cell culture (Bouldin et al, 2015;Garriock et al, 2015;Gouti et al, 2014;Henrique et al, 2015;Jurberg et al, 2014;Martin and Kimelman, 2012;Tsakiridis et al, 2014), our data indicate that Wnt signaling has a conserved role in the induction of all tailbud mesoderm from discrete bipotential neuromesodermal progenitors. As in PWPCs, Wnt induces mesodermal fate through repression of sox2 expression.…”

Section: Two Populations Of Mpcs In the Tailbudsupporting

confidence: 65%

“…In the posterior wall of the tailbud and in cell culture, Wnt signaling induces new mesoderm from PWPCs (Bouldin et al, 2015;Garriock et al, 2015;Gouti et al, 2014;Henrique et al, 2015;Jurberg et al, 2014;Martin and Kimelman, 2012;Tsakiridis et al, 2014). To determine whether Wnt signaling also induces new mesoderm formation within the tailbud MPCs, we used heat shockinducible transgenic lines to temporally inhibit (hsp70l:TCFΔC-GFP) or activate (hsp70l:β-Catenin-TFP) Wnt signaling (Martin and Kimelman, 2012;Veldman et al, 2013).…”

Section: Resultsmentioning

confidence: 99%

“…Recent work demonstrated that the caudalmost progenitors within the tailbud, the posterior wall progenitor cells (PWPCs; sometimes referred to as neuromesodermal progenitors), are bipotential and continuously make neural/mesodermal fate decisions during embryo elongation. (Freese et al, 2014;Garriock et al, 2015;Gentsch et al, 2013;Gouti et al, 2014;Kondoh and Takemoto, 2012;Martin and Kimelman, 2012;Tzouanacou et al, 2009). These cells give rise to the growing spinal cord, somites and vasculature.…”

Section: Introductionmentioning

confidence: 99%

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The zebrafish tailbud contains two independent populations of midline progenitor cells that maintain long-term germ layer plasticity and differentiate based on local signaling cues

et al. 2015

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Vertebrate body axis formation depends on a population of bipotential neuromesodermal cells along the posterior wall of the tailbud that make a germ layer decision after gastrulation to form spinal cord and mesoderm. Despite exhibiting germ layer plasticity, these cells never give rise to midline tissues of the notochord, floor plate and dorsal endoderm, raising the question of whether midline tissues also arise from basal posterior progenitors after gastrulation. We show in zebrafish that local posterior signals specify germ layer fate in two basal tailbud midline progenitor populations. Wnt signaling induces notochord within a population of notochord/floor plate bipotential cells through negative transcriptional regulation of sox2. Notch signaling, required for hypochord induction during gastrulation, continues to act in the tailbud to specify hypochord from a notochord/hypochord bipotential cell population. Our results lend strong support to a continuous allocation model of midline tissue formation in zebrafish, and provide an embryological basis for zebrafish and mouse bifurcated notochord phenotypes as well as the rare human congenital split notochord syndrome. We demonstrate developmental equivalency between the tailbud progenitor cell populations. Midline progenitors can be transfated from notochord to somite fate after gastrulation by ectopic expression of msgn1, a master regulator of paraxial mesoderm fate, or if transplanted into the bipotential progenitors that normally give rise to somites. Our results indicate that the entire non-epidermal posterior body is derived from discrete, basal tailbud cell populations. These cells remain receptive to extracellular cues after gastrulation and continue to make basic germ layer decisions.

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Section: Two Populations Of Mpcs In the Tailbudsupporting

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The zebrafish tailbud contains two independent populations of midline progenitor cells that maintain long-term germ layer plasticity and differentiate based on local signaling cues

et al. 2015

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“…To elucidate the potential role of Sp5/8 as transcriptional effectors of the Wnt/ β-catenin pathway, we overexpressed Sp8 (13) in NMPs, in vivo, using the T-Cre driver, and a Cre-activated B6.Cg-Gt(ROSA) 26Sortm1(rtTA,EGFP)Nagy/J (rtTA)-expressing mouse line (4,14) (i.e., T-Cre;Sp8 GOF ) and assayed for the expression of several wellestablished Wnt/β-catenin target genes, including T (15), Sp5 (16), and Axin2 (17). T-Cre;Sp8 GOF embryos showed a dramatic expansion of T, which is indicative of an expanded embryonic posterior progenitor population, as well as highly elevated expression of the universal Wnt/β-catenin target genes, Axin2 and Sp5 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Secreted Wnts emanating from the primitive streak regulate the fate of posterior progenitors, including the neuromesodermal progenitor (NMP), an embryonic cell that depends upon Wnt3a for self-renewal and mesodermal differentiation and that gives rise to the spinal cord, dermis, and musculoskeletal system of the trunk and tail (4)(5)(6). Embryos lacking Wnt3a, Ctnnb1 (β-catenin), T-cell factor (Tcf) 1 and lymphoid enhancer factor (Lef) 1, or specificity protein (Sp) 5 and Sp8 display similar severe posterior truncations caused by the loss of NMPs (7)(8)(9)(10).…”

mentioning

confidence: 99%

Sp5 and Sp8 recruit β-catenin and Tcf1-Lef1 to select enhancers to activate Wnt target gene transcription

Kennedy

Chalamalasetty

Thomas

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The ancient, highly conserved, Wnt signaling pathway regulates cell fate in all metazoans. We have previously shown that combined null mutations of the specificity protein (Sp) 1/Klf-like zinc-finger transcription factors Sp5 and Sp8 (i.e., Sp5/8) result in an embryonic phenotype identical to that observed when core components of the Wnt/β-catenin pathway are mutated; however, their role in Wnt signal transduction is unknown. Here, we show in mouse embryos and differentiating embryonic stem cells that Sp5/8 are gene-specific transcriptional coactivators in the Wnt/β-catenin pathway. Sp5/8 bind directly to GC boxes in Wnt target gene enhancers and to adjacent, or distally positioned, chromatin-bound T-cell factor (Tcf) 1/lymphoid enhancer factor (Lef) 1 to facilitate recruitment of β-catenin to target gene enhancers. Because Sp5 is itself directly activated by Wnt signals, we propose that Sp5 is a Wnt/β-catenin pathway-specific transcripton factor that functions in a feed-forward loop to robustly activate select Wnt target genes.S ignaling pathways in multicellular organisms have evolved over millions of years to accommodate complex programs of tissue-specific gene expression. One such pathway, the Wnt/ β-catenin pathway, regulates gene expression by elevating the cytosolic levels of the transcription coactivator β-catenin (1). Stabilized β-catenin translocates to the nucleus, where it interacts with the DNA-bending, DNA-binding Tcf1 and Lef1 transcription factors (TFs), which subsequently replace Groucho/ Tcf3 repressor complexes on Wnt target gene enhancers (2). β-Catenin interacts with cell context-dependent cofactors (web. stanford.edu/group/nusselab/cgi-bin/wnt/) to associate with RNA polymerase II and the general transcription apparatus to activate transcription. However, the nature of the β-cateninTcf/Lef enhancer-binding protein complex and the mechanisms that facilitate its association with regulatory elements at Wnt target genes remain poorly understood.The formation of a Wnt signaling center during gastrulation is essential for animal development (3). Secreted Wnts emanating from the primitive streak regulate the fate of posterior progenitors, including the neuromesodermal progenitor (NMP), an embryonic cell that depends upon Wnt3a for self-renewal and mesodermal differentiation and that gives rise to the spinal cord, dermis, and musculoskeletal system of the trunk and tail (4-6). Embryos lacking Wnt3a, Ctnnb1 (β-catenin), T-cell factor (Tcf) 1 and lymphoid enhancer factor (Lef) 1, or specificity protein (Sp) 5 and Sp8 display similar severe posterior truncations caused by the loss of NMPs (7-10). These genes define a syn-phenotype group that, together with the genetic interactions observed between Sp5 and Wnt3a, suggests that Sp5/8 could be effectors of Wnt signaling. Sp5/8 are closely related to Sp1, which is one of the first identified eukaryotic TFs (11) and is frequently associated with the regulation of housekeeping genes. In contrast to the ubiquitously expressed Sp1, Sp5 expression is restricte...

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A novel cold‐sensitive mutant of ntla reveals temporal roles of brachyury in zebrafish

Kimelman¹

2016

Developmental Dynamics

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Background With the exception of the head, the vertebrate embryonic body is formed progressively in an anterior-posterior direction, originating from a posteriorly located bipotential neural-mesodermal progenitor population. The T-box transcription factor Brachyury is expressed within the progenitors, and is essential for the formation of the posterior mesoderm. A novel cold-sensitive mutant of zebrafish Brachyury (ntlacs) is described that allows exploration of the temporal role of this key factor. Results The ntlacs mutant is used to show that Ntla has an essential role during early gastrulation, but as gastrulation proceeds the importance of Ntla declines as Ntlb acquires a capacity to form the posterior mesoderm. Remarkably, ntlacs embryos held at the non-permissive temperature just during the gastrula stages show recovery of normal levels of mesodermal gene expression, demonstrating the plasticity of the posterior progenitors. Conclusion ntlacs is a valuable tool for exploring the processes forming the posterior body since it allows temporally specific activation and inactivation of Brachyury function. It is used here to show the changing roles of Ntla during early development, and the dynamics of the neuromesdermal progenitors.

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Lineage tracing of neuromesodermal progenitors reveals novel Wnt-dependent roles in trunk progenitor cell maintenance and differentiation

Cited by 115 publications

References 48 publications

The zebrafish tailbud contains two independent populations of midline progenitor cells that maintain long-term germ layer plasticity and differentiate based on local signaling cues

The zebrafish tailbud contains two independent populations of midline progenitor cells that maintain long-term germ layer plasticity and differentiate based on local signaling cues

Sp5 and Sp8 recruit β-catenin and Tcf1-Lef1 to select enhancers to activate Wnt target gene transcription

A novel cold‐sensitive mutant of ntla reveals temporal roles of brachyury in zebrafish

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