Biology subjects

Smits, K.

Publications and source records attributed to Smits, K..

3 recordsLinked to original sources

bioRxiv2024

Mechanistic origin and preimplantation development of uniparental and polyploid blastomeres

Whole-genome (WG) abnormalities, such as uniparental diploidy and triploidy, cause fetal death. Occasionally, they coexist with biparental diploid cells in live births. Understanding the origin and early development of WG abnormal blastomeres is crucial for explaining the formation of androgenotes, gynogenotes, triploidy, chimerism, and mixoploidy. By haplotyping 118 blastomeres from first cleavages, we identified various mechanisms of heterogoneic divisions that lead to WG abnormal blastomeres or their coexistence with normal blastomeres in both multipolar and bipolar cleaving zygotes. After culturing the totipotent blastomeres to three preimplantation stages and performing transcriptome profiling on over 600 cells, we discovered that stress responses contribute to developmental impairment in WG abnormal cells, resulting in either cell arrest or blastocyst formation. Some first-cleavage-derived WG abnormal blastomeres can survive early development and progress to blastocysts. Their potential dominance in preimplantation embryos represents an overlooked cause of abnormal development. Haplotype based screening could further increase pregnancy rates.

genetics↗

bioRxiv2021

Parental genomes segregate into different blastomeres during multipolar zygotic divisions leading to mixoploid and chimeric blastocysts

The zygotic division enables two haploid genomes to segregate into two biparental diploid blastomeres. This fundamental tenet was challenged by the observation that blastomeres with different genome ploidy or parental genotypes can coexist within individual embryos. We hypothesized that whole parental genomes can segregate into distinct blastomere lineages during the first division through "heterogoneic division". Here, we map the genomic landscape of 82 blastomeres from 25 embryos that underwent multipolar zygotic division. The coexistence of androgenetic and diploid or polyploid blastomeres with or without anuclear blastomeres, and androgenetic and gynogenetic blastomeres within the same embryo proofs the existence of heterogoneic division. We deduced distinct segregation mechanisms and demonstrate these genome-wide segregation errors to persist to the blastocyst stage in both human and cattle. Genome-wide zygotic segregation errors contribute to the high incidence of embryonic arrest and provide an overarching paradigm for the development of mixoploid and chimeric individuals and moles.

developmental biology↗

bioRxiv2020

Visual stimulus-specific habituation of innate defensive behaviour in mice

Innate defensive responses such as freezing or escape are essential for animal survival. Mice show defensive behaviour to stimuli sweeping overhead, like a bird cruising the sky. Here, we found that mice reduced their defensive freezing after sessions with a stimulus passing overhead repeatedly. This habituation is stimulus-specific, as mice freeze again to a novel shape. This allows us to investigate the invariances in the mouse visual system. The mice generalize over retinotopic location and over size and shape, but distinguish objects when they differ in both size and shape. Innate visual defensive responses are thus strongly influenced by previous experience as mice learn to ignore specific stimuli. This form of learning occurs at the level of a location-independent representation.

neuroscience↗