Biomedical subjects

Aitana Perea-Gomez

Publications and source records attributed to Aitana Perea-Gomez.

6 recordsLinked to original sources

PubMed2025

Ovarian development is driven by early spatiotemporal priming of the coelomic epithelium.

Ovarian organogenesis requires the coordinated specification of supporting and steroidogenic cell lineages from multipotent coelomic epithelium (CE) progenitors. A longstanding question is whether the CE contains transcriptionally distinct, spatially organized progenitor subpopulations with predetermined lineage biases, or whether specification into supporting and steroidogenic lineages occurs only after delamination and integration into the bipotential gonad. The developmental origins of granulosa cells and the emergence of ovarian steroidogenic/stromal progenitors (SPs) also remain poorly defined. Here, we show that CE cells covering the fetal mouse ovary are transcriptionally heterogeneous and spatially organized into subdomains already primed toward supporting or steroidogenic fates. CE priming is dynamic, with transient coexistence of supporting- and steroidogenic-biased CE progenitors before resolving into a predominantly supporting-biased CE. Local delamination of these primed cells seeds intragonadal niches where pre-granulosa cells and SPs mirror the spatio-temporal arrangements of CE-primed progenitors. We further demonstrate a dual origin for the supporting lineage, with granulosa cells deriving from both the CE and supporting-like cells (SLCs). In parallel, we show that SPs arise from steroidogenic-primed CE cells, expand to represent 52% of ovarian somatic cells at birth, persist into adulthood and contribute to both theca and steroidogenic stromal cells. Together, these findings reveal transcriptionally and spatially distinct CE subpopulations that shape somatic lineage emergence with important implications for ovarian pathophysiology.

Ovarian development↗

PubMed2006

Absence of Nodal signaling promotes precocious neural differentiation in the mouse embryo.

After implantation, mouse embryos deficient for the activity of the transforming growth factor-beta member Nodal fail to form both the mesoderm and the definitive endoderm. They also fail to specify the anterior visceral endoderm, a specialized signaling center which has been shown to be required for the establishment of anterior identity in the epiblast. Our study reveals that Nodal-/- epiblast cells nevertheless express prematurely and ectopically molecular markers specific of anterior fate. Our analysis shows that neural specification occurs and regional identities characteristic of the forebrain are established precociously in the Nodal-/- mutant with a sequential progression equivalent to that of wild-type embryo. When explanted and cultured in vitro, Nodal-/- epiblast cells readily differentiate into neurons. Genes normally transcribed in organizer-derived tissues, such as Gsc and Foxa2, are also expressed in Nodal-/- epiblast. The analysis of Nodal-/-;Gsc-/- compound mutant embryos shows that Gsc activity plays no critical role in the acquisition of forebrain characters by Nodal-deficient cells. This study suggests that the initial steps of neural specification and forebrain development may take place well before gastrulation in the mouse and highlights a possible role for Nodal, at pregastrula stages, in the inhibition of anterior and neural fate determination.

Animals↗

PubMed2005

Four-cell stage mouse blastomeres have different developmental properties.

Blastomeres of the early mouse embryo are thought to be equivalent in their developmental properties at least until the eight-cell stage. However, the experiments that have led to this conclusion could not have taken into account either the spatial origin of individual blastomeres or the spatial allocation and fate of their progeny. We have therefore readdressed this issue having defined cell lineages in mouse embryos undergoing different patterns of cleavage in their second division cycle. This has enabled us to identify a major group of embryos in which we can predict not only the spatial origin of each given four-cell blastomeres, but also which region of the blastocyst is most likely to be occupied by its progeny. We show that a pattern of second cleavage divisions in which a meridional division is followed by one that is equatorial or oblique allows us to identify blastomeres that differ in their fate and in their developmental properties both from each other and from their cousins. We find that one of these four-cell stage blastomeres that inherits some vegetal membrane marked in the previous cleavage cycle tends to contribute to mural trophectoderm. The progeny of its sister tend to donate cells to part of the ICM lining the blastocyst cavity and its associated trophectoderm. Chimaeras made entirely of these equatorially or obliquely derived blastomeres show developmental abnormalities in both late preimplantation and early postimplantation development. By contrast, chimaeras made from four-cell stage blastomeres from early meridional divisions develop normally. The developmental defects of chimaeras made from the most vegetal blastomeres that result from later second cleavages are the most severe and following transplantation into foster mothers they fail to develop to term. However, when such individual four-cell blastomeres are surrounded by blastomeres from random positions, they are able to contribute to all embryonic lineages. In conclusion, this study shows that while all four-cell blastomeres can have full developmental potential, they differ in their individual developmental properties according to their origin in the embryo from as early as the four-cell stage.

Animals↗

PubMed2004

Nodal antagonists regulate formation of the anteroposterior axis of the mouse embryo.

Patterning of the mouse embryo along the anteroposterior axis during body plan development requires migration of the distal visceral endoderm (DVE) towards the future anterior side by a mechanism that has remained unknown. Here we show that Nodal signalling and the regionalization of its antagonists are required for normal migration of the DVE. Whereas Nodal signalling provides the driving force for DVE migration by stimulating the proliferation of visceral endoderm cells, the antagonists Lefty1 and Cerl determine the direction of migration by asymmetrically inhibiting Nodal activity on the future anterior side.

Animals↗

PubMed2004

Initiation of gastrulation in the mouse embryo is preceded by an apparent shift in the orientation of the anterior-posterior axis.

BACKGROUND: It is generally assumed that the migration of anterior visceral endoderm (AVE) cells from a distal to a proximal position at embryonic day (E)5.5 breaks the radial symmetry of the mouse embryo, marks anterior, and conditions the formation of the primitive streak on the opposite side at E6.5. Transverse sections of a gastrulating mouse embryo fit within the outline of an ellipse, with the primitive streak positioned at one end of its long axis. How the establishment of anterior-posterior (AP) polarity relates to the morphology of the postimplantation embryo is, however, unclear. RESULTS: Transverse sections of prestreak E6.0 embryos also reveal an elliptical outline, but the AP axis, defined by molecular markers, tends to be perpendicular to the long axis of the ellipse. Subsequently, the relative orientations of the AP axis and of the long axis change so that when gastrulation begins, they are closer to being parallel, albeit not exactly aligned. As a result, most embryos briefly lose their bilateral symmetry when the primitive streak starts forming in the epiblast. CONCLUSIONS: The change in the orientation of the AP axis is only apparent and results from a dramatic remodeling of the whole epiblast, in which cell migrations take no part. These results reveal a level of regulation and plasticity so far unsuspected in the mouse gastrula.

Animals↗

PubMed2002

Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks.

The anterior visceral endoderm plays a pivotal role in establishing anterior-posterior polarity of the mouse embryo, but the molecular nature of the signals required remains to be determined. Here, we demonstrate that Cerberus-like(-/-);Lefty1(-/-) compound mutants can develop a primitive streak ectopically in the embryo. This defect is not rescued in chimeras containing wild-type embryonic, and Cerberus-like(-/-);Lefty1(-/-) extraembryonic, cells but is rescued in Cerberus-like(-/-); Lefty1(-/-) embryos after removal of one copy of the Nodal gene. Our findings provide support for a model whereby Cerberus-like and Lefty1 in the anterior visceral endoderm restrict primitive streak formation to the posterior end of mouse embryos by antagonizing Nodal signaling. Both antagonists are also required for proper patterning of the primitive streak.

Animals↗