Biology subjects

Abreu, J. G.

Publications and source records attributed to Abreu, J. G..

3 recordsLinked to original sources

bioRxiv2025

Cell division during Xenopus gastrulation influences neuroectoderm patterning

Oriented cell division is essential for establishing the anterior-posterior body (A-P) axis in diverse species. However, in Xenopus laevis, blocking cell division during gastrulation does not impair the development of the neural tube and body elongation. Here, we demonstrate that neither neurulation nor dorsal mesoderm formation is dependent on cell division. On the other hand, neural plate elongation and A-P patterning are impacted in the absence of cell division, resulting in trunk defects and anterior defects that appear during tailbud stages. We also show that cell division is abundant around the ectoderm of the gastrulating embryo. Still, it is more intense in the dorsal ectoderm (presumptive neural plate), where there is a clear preference for A-P oriented cell divisions. Taken together, our results highlight a conserved mechanism of A-P oriented cell division that is present during neural plate elongation and patterning.

developmental biology↗

bioRxiv2025

High doses of electromagnetic radiation pre- and post- fertilization produce different developmental outcomes in Xenopus laevis.

We examined the effects of X-ray irradiation on Xenopus laevis, focusing on pre- and post-fertilization exposure. We applied X-ray doses of 10, 50, 100, 250, and 500 Gy. Fifty percent of the 360 eggs irradiated at 250 Gy failed to fertilize, while fertilized eggs developed normally until the gastrula stage. Doses ranging from 10 to 250 Gy caused developmental anomalies. High mortality rates were observed at doses of 100 to 500 Gy. Post-fertilization irradiation at 50 to 100 Gy resulted in 100% lethality, while exposure to 10 Gy led to only 13% lethality, although both exposure levels produced similar types of developmental anomalies compared to pre-fertilization irradiation. This study highlights how the timing and intensity of exposure critically affect embryo viability, especially during the sensitive stages of fertilization and gastrulation. We establish the necessary and sufficient dosage to further investigate the molecular mechanisms of X-ray damage to DNA and protein. HighlightHigh doses of electromagnetic radiation pre- and post-fertilization produce different developmental outcomes in Xenopus laevis.

pharmacology and toxicology↗

bioRxiv2019

Depletion of Ric-8B leads to reduced mTORC2 activity

mTOR, a serine/threonine protein kinase that is involved in a series of critical cellular processes, can be found in two functionally distinct complexes, mTORC1 and mTORC2. In contrast to mTORC1, little is known about the mechanisms that regulate mTORC2. Here we show that mTORC2 activity is reduced in mice with a hypomorphic mutation of the Ric-8B gene. Ric-8B is a highly conserved protein that acts as a non-canonical guanine nucleotide exchange factor (GEF) for heterotrimeric Gs/olf type subunits. We found that Ric-8B hypomorph embryos are smaller than their wild type littermates, fail to close the neural tube in the cephalic region and die during mid-embryogenesis. Comparative transcriptome analysis revealed that signaling pathways involving GPCRs and G proteins are dysregulated in the Ric-8B mutant embryos. Interestingly, this analysis also revealed an unexpected impairment of the mTOR signaling pathway.\n\nPhosphorylation of Akt at Ser 473 is downregulated in the Ric-8B mutant embryos, indicating a decreased activity of mTORC2. In contrast, phosphorylation of S6, a downstream target of mTORC1, is unaltered. Knockdown of the endogenous Ric-8B gene in HEK293T cells leads to reduced phosphorylation levels of Akt at Ser 473, but not of S6, further supporting the selective involvement of Ric-8B in mTORC2 activity. Our results reveal a crucial role for Ric-8B in development and provide novel insights into the signals that regulate mTORC2 activity.\n\nAuthor SummaryGene inactivation in mice can be used to identify genes that are involved in important biological processes and that may contribute to disease. By using this approach, we found that the Ric-8B gene is essential for embryogenesis and for the normal development of the nervous system. Ric-8B mutant mouse embryos are smaller than their wild type littermates and show neural tube defects at the cranial region. This approach also allowed us to identify the biological pathways that are involved in the observed phenotypes, the G protein and mTORC2 signaling pathways. mTORC2 plays particular important roles also in the adult brain, and has been implicated in neurological disorders. Ric-8B is highly conserved in mammals, including humans. Our mutant mice provide a model to study the complex molecular and cellular processes underlying the interplay between Ric-8B and mTORC2 in neuronal function.

molecular biology↗