Cargando…

Correct Patterning of the Primitive Streak Requires the Anterior Visceral Endoderm

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 demons...

Descripción completa

Detalles Bibliográficos
Autores principales: Stuckey, Daniel W., Di Gregorio, Aida, Clements, Melanie, Rodriguez, Tristan A.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060820/
https://www.ncbi.nlm.nih.gov/pubmed/21445260
http://dx.doi.org/10.1371/journal.pone.0017620
_version_ 1782200543095029760
author Stuckey, Daniel W.
Di Gregorio, Aida
Clements, Melanie
Rodriguez, Tristan A.
author_facet Stuckey, Daniel W.
Di Gregorio, Aida
Clements, Melanie
Rodriguez, Tristan A.
author_sort Stuckey, Daniel W.
collection PubMed
description 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.
format Text
id pubmed-3060820
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-30608202011-03-28 Correct Patterning of the Primitive Streak Requires the Anterior Visceral Endoderm Stuckey, Daniel W. Di Gregorio, Aida Clements, Melanie Rodriguez, Tristan A. PLoS One Research Article 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. Public Library of Science 2011-03-18 /pmc/articles/PMC3060820/ /pubmed/21445260 http://dx.doi.org/10.1371/journal.pone.0017620 Text en Stuckey et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Stuckey, Daniel W.
Di Gregorio, Aida
Clements, Melanie
Rodriguez, Tristan A.
Correct Patterning of the Primitive Streak Requires the Anterior Visceral Endoderm
title Correct Patterning of the Primitive Streak Requires the Anterior Visceral Endoderm
title_full Correct Patterning of the Primitive Streak Requires the Anterior Visceral Endoderm
title_fullStr Correct Patterning of the Primitive Streak Requires the Anterior Visceral Endoderm
title_full_unstemmed Correct Patterning of the Primitive Streak Requires the Anterior Visceral Endoderm
title_short Correct Patterning of the Primitive Streak Requires the Anterior Visceral Endoderm
title_sort correct patterning of the primitive streak requires the anterior visceral endoderm
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060820/
https://www.ncbi.nlm.nih.gov/pubmed/21445260
http://dx.doi.org/10.1371/journal.pone.0017620
work_keys_str_mv AT stuckeydanielw correctpatterningoftheprimitivestreakrequirestheanteriorvisceralendoderm
AT digregorioaida correctpatterningoftheprimitivestreakrequirestheanteriorvisceralendoderm
AT clementsmelanie correctpatterningoftheprimitivestreakrequirestheanteriorvisceralendoderm
AT rodrigueztristana correctpatterningoftheprimitivestreakrequirestheanteriorvisceralendoderm