Response to BMP4 signalling during ES cell differentiation defines intermediates of the ectoderm lineage

Harvey, Nathan T.; Hughes, James; Lonic, Ana; Yap, Charlotte; Long, Catherine; Rathjen, Peter D.; Rathjen, Joy

doi:10.1242/jcs.047530

“…This observation is consistent with previous studies showing that p63 induction of epidermal keratinocyte fate in mouse ESCs requires BMP4 signaling (Medawar et al, 2008). Additionally, BMP signaling can induce ectodermal fate in hESCs Harvey et al, 2010) and in surface ectoderm progenitors of Xenopus embryos (Wilson and Hemmati-Brivanlou, 1995). Wnt signals can also promote surface ectoderm fate and repress neuroectoderm fate (Wilson et al, 2001).…”

Section: Research Articlesupporting

confidence: 92%

Notch signaling represses p63 expression in the developing surface ectoderm

Tadeu

¹

,

Horsley

²

2013

View full text Add to dashboard Cite

MiceK14-H2BGFP transgenic mice (Tumbar et al., 2004) SUMMARYThe development of the mature epidermis requires a coordinated sequence of signaling events and transcriptional changes to specify surface ectodermal progenitor cells to the keratinocyte lineage. The initial events that specify epidermal keratinocytes from ectodermal progenitor cells are not well understood. Here, we use both developing mouse embryos and human embryonic stem cells (hESCs) to explore the mechanisms that direct keratinocyte fate from ectodermal progenitor cells. We show that both hESCs and murine embryos express p63 before keratin 14. Furthermore, we find that Notch signaling is activated before p63 expression in ectodermal progenitor cells. Inhibition of Notch signaling pharmacologically or genetically reveals a negative regulatory role for Notch signaling in p63 expression during ectodermal specification in hESCs or mouse embryos, respectively. Taken together, these data reveal a role for Notch signaling in the molecular control of ectodermal progenitor cell specification to the epidermal keratinocyte lineage.

show abstract

“…The addition of BMP4, in BMP4-containing medium (BCM; supplementary material Table S1), or serum, in serum-containing medium (SCM; supplementary material Table S1), during differentiation resulted in the formation of cardiocytes and erthryocytes within the aggregates, as expected from previous analyses of differentiation (Fig. 1B) (Harvey et al, 2010;Zheng et al, 2010). The addition of SB to serum reduced the percentage of aggregates that formed erthryocytes and increased the percentage of aggregates that formed neurons, whereas cardiocyte formation was unaffected (Fig.…”

Section: Bmp4 and Serum Induce The Formation Of Primitive Streak Intesupporting

confidence: 77%

The formation of proximal and distal definitive endoderm populations in culture requires p38 MAPK activity

Yap

¹

,

Goh

²

,

Familari

³

et al. 2014

Self Cite

View full text Add to dashboard Cite

BSTRACTEndoderm formation in the mammal is a complex process with two lineages forming during the first weeks of development, the primitive (or extraembryonic) endoderm, which is specified in the blastocyst, and the definitive endoderm that forms later, at gastrulation, as one of the germ layers of the embryo proper. Fate mapping evidence suggests that the definitive endoderm arises as two waves, which potentially reflect two distinct cell populations. Early primitive ectoderm-like (EPL) cell differentiation has been used successfully to identify and characterise mechanisms regulating molecular gastrulation and lineage choice during differentiation. The roles of the p38 MAPK family in the formation of definitive endoderm were investigated using EPL cells and chemical inhibitors of p38 MAPK activity. These approaches define a role for p38 MAPK activity in the formation of the primitive streak and a second role in the formation of the definitive endoderm. Characterisation of the definitive endoderm populations formed from EPL cells demonstrates the formation of two distinct populations, defined by gene expression and ontogeny, that were analogous to the proximal and distal definitive endoderm populations of the embryo. Formation of the proximal definitive endoderm was found to require p38 MAPK activity and is correlated with molecular gastrulation, defined by the expression of brachyury (T). Distal definitive endoderm formation also requires p38 MAPK activity but can form when T expression is inhibited. Understanding lineage complexity will be a prerequisite for the generation of endoderm derivatives for commercial and clinical use.

show abstract

“…Primitive streak intermediates can be induced from EPL cells by BMP4 (Harvey et al, 2010;Zheng et al, 2010) or serum (Hughes et al, 2009b). The requirement for p38 MAPK activity in the formation of primitive streak intermediates in response to these inducers was investigated.…”

Section: Bmp4 and Serum Induce The Formation Of Primitive Streak Intementioning

confidence: 99%

“…+ and Gata4 + endoderm in response to BMP4 is a two-step process proceeding through a bipotent primitive streak intermediate, or mesendoderm. The likely role for BMP4 in this process is indirect, by way of the induction of mesendoderm from EPL cells (Harvey et al, 2010). The possibility exists, however, that BMP4 has a role in the subsequent induction of endoderm from mesendoderm.…”

Section: Bmp4 and Serum Induce The Formation Of Primitive Streak Intementioning

confidence: 99%

“…Using EPL cells as the starting material for differentiation has resulted in a reliable model of gastrulation, which has been used to determine the role of growth factors, environmental manipulations and intracellular signalling in cell differentiation and to allow the identification of transient developmental intermediates (Harvey et al, 2010;Hughes et al, 2009a;Hughes et al, 2009b;Zheng et al, 2010). Here, the differentiation of EPL cells is used to investigate the control of molecular gastrulation, with a focus on the formation of definitive endoderm.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The formation of proximal and distal definitive endoderm populations in culture requires p38 MAPK activity

Yap

¹

,

Goh

²

,

Familari

³

et al. 2014

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

BSTRACTEndoderm formation in the mammal is a complex process with two lineages forming during the first weeks of development, the primitive (or extraembryonic) endoderm, which is specified in the blastocyst, and the definitive endoderm that forms later, at gastrulation, as one of the germ layers of the embryo proper. Fate mapping evidence suggests that the definitive endoderm arises as two waves, which potentially reflect two distinct cell populations. Early primitive ectoderm-like (EPL) cell differentiation has been used successfully to identify and characterise mechanisms regulating molecular gastrulation and lineage choice during differentiation. The roles of the p38 MAPK family in the formation of definitive endoderm were investigated using EPL cells and chemical inhibitors of p38 MAPK activity. These approaches define a role for p38 MAPK activity in the formation of the primitive streak and a second role in the formation of the definitive endoderm. Characterisation of the definitive endoderm populations formed from EPL cells demonstrates the formation of two distinct populations, defined by gene expression and ontogeny, that were analogous to the proximal and distal definitive endoderm populations of the embryo. Formation of the proximal definitive endoderm was found to require p38 MAPK activity and is correlated with molecular gastrulation, defined by the expression of brachyury (T). Distal definitive endoderm formation also requires p38 MAPK activity but can form when T expression is inhibited. Understanding lineage complexity will be a prerequisite for the generation of endoderm derivatives for commercial and clinical use.

show abstract

Response to BMP4 signalling during ES cell differentiation defines intermediates of the ectoderm lineage

Cited by 30 publications

References 51 publications

Notch signaling represses p63 expression in the developing surface ectoderm

Notch signaling represses p63 expression in the developing surface ectoderm

The formation of proximal and distal definitive endoderm populations in culture requires p38 MAPK activity

The formation of proximal and distal definitive endoderm populations in culture requires p38 MAPK activity

Contact Info

Product

Resources

About