The DVE changes distal epiblast fate from definitive endoderm to neurectoderm by antagonizing nodal signaling

Miura, Shigeto; Mishina, Yuji

doi:10.1002/dvdy.21166

Cited by 7 publications

(6 citation statements)

References 43 publications

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“…Microsurgical ablation of the AVE at the onset of gastrulation leads to forebrain truncations [10] and ablation at 5.5dpc abolishes the expression of anterior neuroectoderm markers [11]. Analysis of mouse mutants where gene function has been specifically lost in extra-embryonic tissues has further demonstrated the role of the AVE in forebrain specification [12], [13], [14].…”

Section: Introductionmentioning

confidence: 99%

Correct Patterning of the Primitive Streak Requires the Anterior Visceral Endoderm

et al. 2011

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Anterior-posterior axis specification in the mouse requires signalling from a specialised extra-embryonic tissue called the anterior visceral endoderm (AVE). AVE precursors are induced at the distal tip of the embryo and move to the prospective anterior. Embryological and genetic analysis has demonstrated that the AVE is required for anterior patterning and for correctly positioning the site of primitive streak formation by inhibiting Nodal activity. We have carried out a genetic ablation of the Hex-expressing cells of the AVE (Hex-AVE) by knocking the Diphtheria toxin subunit A into the Hex locus in an inducible manner. Using this model we have identified that, in addition to its requirement in the anterior of the embryo, the Hex-AVE sub-population has a novel role between 5.5 and 6.5dpc in patterning the primitive streak. Embryos lacking the Hex-AVE display delayed initiation of primitive streak formation and miss-patterning of the anterior primitive streak. We demonstrate that in the absence of the Hex-AVE the restriction of Bmp2 expression to the proximal visceral endoderm is also defective and expression of Wnt3 and Nodal is not correctly restricted to the posterior epiblast. These results, coupled with the observation that reducing Nodal signalling in Hex-AVE ablated embryos increases the frequency of phenotypes observed, suggests that these primitive streak patterning defects are due to defective Nodal signalling. Together, our experiments demonstrate that the AVE is not only required for anterior patterning, but also that specific sub-populations of this tissue are required to pattern the posterior of the embryo.

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Section: Introductionmentioning

confidence: 99%

Correct Patterning of the Primitive Streak Requires the Anterior Visceral Endoderm

et al. 2011

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“…The leading role of the primary AVE was suggested through microsurgical ablation of the primary AVE, which resulted in a wider defect in remaining VE migration (Miura and Mishina 2007). Importantly, inducible genetic lineage ablation of Lefty1 -expressing cells clearly showed that the secondary AVE does not migrate anteriorly if early Lefty1 -expressing primitive endoderm is eliminated (Takaoka et al 2011).…”

Section: Anteroposterior Axis Patterningmentioning

confidence: 99%

Vertebrate Axial Patterning: From Egg to Asymmetry

Houston

2016

Advances in Experimental Medicine and Biology

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The emergence of the bilateral embryonic body axis from a symmetrical egg has been a long-standing question in developmental biology. Historical and modern experiments point to an initial symmetry-breaking event leading to localized Wnt and Nodal growth factor signaling and subsequent induction and formation of a self-regulating dorsal "organizer." This organizer forms at the site of notochord cell internalization and expresses primarily Bone Morphogenetic Protein (BMP) growth factor antagonists that establish a spatiotemporal gradient of BMP signaling across the embryo, directing initial cell differentiation and morphogenesis. Although the basics of this model have been known for some time, many of the molecular and cellular details have only recently been elucidated and the extent that these events remain conserved throughout vertebrate evolution remains unclear. This chapter summarizes historical perspectives as well as recent molecular and genetic advances regarding: (1) the mechanisms that regulate symmetry-breaking in the vertebrate egg and early embryo, (2) the pathways that are activated by these events, in particular the Wnt pathway, and the role of these pathways in the formation and function of the organizer, and (3) how these pathways also mediate anteroposterior patterning and axial morphogenesis. Emphasis is placed on comparative aspects of the egg-to-embryo transition across vertebrates and their evolution. The future prospects for work regarding self-organization and gene regulatory networks in the context of early axis formation are also discussed.

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“…AVE ablation experiments and disruption of gene function specifically in the VE lead to forebrain truncations, indicating that the function of the AVE is essential for head development (Arkell and Tam, 2012;Miura and Mishina, 2007;Rhinn et al, 1998;Shawlot et al, 1999;Stern and Downs, 2012;Stuckey et al, 2011b;Thomas and Beddington, 1996;Varlet et al, 1997). AVE ablation experiments and disruption of gene function specifically in the VE lead to forebrain truncations, indicating that the function of the AVE is essential for head development (Arkell and Tam, 2012;Miura and Mishina, 2007;Rhinn et al, 1998;Shawlot et al, 1999;Stern and Downs, 2012;Stuckey et al, 2011b;Thomas and Beddington, 1996;Varlet et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…However, explant recombination experiments and tissue grafts failed to uncover any anterior neural inducing activity of AVE cells. This could contribute to protecting these precursors from the influence of primitive streak derived signals (Miura and Mishina, 2007). Is there an additional role for DVE and AVE cells in controlling head development?…”

Section: Introductionmentioning

confidence: 99%