Biology subjects

Aguera-Gonzalez, S.

Publications and source records attributed to Aguera-Gonzalez, S..

2 recordsLinked to original sources

bioRxiv2026

Choreographed morphogenetic events underlie early foregut development in the mouse embryo

Between embryonic days 7.5 and 8.5, the mouse embryo undergoes a dramatic rearrangement of its entire anterior, a process known as ventral folding: the near-simultaneous morphogenesis of the cardiac crescent, cranial headfolds, and anterior foregut that together establish the antero-ventral body plan. While cardiac morphogenesis has been studied in detail, the cellular and mechanical basis of foregut involution remains largely undefined. Using combined light-sheet and spinning-disk live imaging spanning the full window of foregut formation, we show that involution proceeds through a stereotyped morphological programme that does not require actomyosin contractility for its initiation. Additionally, involution is preceded by a spatiotemporally restricted wave of apoptosis in embryonic visceral endoderm (emVE) cells, which extrude bidirectionally. A lineage- and stage-resolved bulk RNA-sequencing of emVE, definitive endoderm, and epiblast populations identifies a differential-adhesion and cell-cycle signature underlying this behaviour. Revisiting a visceral-endoderm-specific Bmp2 knock-out mutant, we find that BMP2 controls involution indirectly, by directing notochord positioning and thereby the geometry of the surrounding heart and headfold mechanics. Together, these findings reframe ventral folding as a single coordinated geometric process rather than a set of independent organ forming events.

developmental biology↗

bioRxiv2020

Compromised nuclear envelope integrity drives tumor cell invasion

While mutations leading to a fragile envelope of the cell nucleus are well known to cause diseases such as muscular dystrophies or accelerated aging, the pathophysiological consequences of the recently discovered mechanically induced nuclear envelope ruptures in cells harboring no mutation are less known. Here we show that repeated loss of nuclear envelope integrity in nuclei experiencing mechanical constraints promotes senescence in nontransformed cells, and induces an invasive phenotype including increased collagen degradation in human breast cancer cells, both in vitro and in a mouse xenograft model of breast cancer progression. We show that these phenotypic changes are due to the presence of chronic DNA damage and activation of the ATM kinase. In addition, we found that depletion of the cytoplasmic exonuclease TREX1 is sufficient to abolish the DNA damage in mechanically challenged nuclei and to suppress the phenotypes associated with the loss of nuclear envelope integrity. Our results also show that TREX1-dependent DNA damage induced by physical confinement of tumor cells inside the mammary duct drives the progression of in situ breast carcinoma to the invasive stage. We propose that DNA damage in mechanically challenged nuclei could affect the pathophysiology of crowded tissues by modulating proliferation and extracellular matrix degradation of normal and transformed cells.

cell biology↗