Mendelian nightmares: the germline-restricted chromosome of songbirds.

Germline-restricted chromosomes (GRCs) are accessory chromosomes that occur only in germ cells. They are eliminated from somatic cells through programmed DNA elimination during embryo development. GRCs have been observed in several unrelated animal taxa and show peculiar modes of non-Mendelian inheritance and within-individual elimination. Recent cytogenetic and phylogenomic evidence suggests that a GRC is present across the species-rich songbirds, but absent in non-passerine birds, implying that over half of all 10,500 bird species have extensive germline/soma genome differences. Here, we review recent insights gained from genomic, transcriptomic, and cytogenetic approaches with regard to the genetic content, phylogenetic distribution, and inheritance of the songbird GRC. While many questions remain unsolved in terms of GRC inheritance, elimination, and function, we discuss plausible scenarios and future directions for understanding this widespread form of programmed DNA elimination.

Application of Fused Organoid Models to Study Human Brain Development and Neural Disorders.

Human brain organoids cultured from human pluripotent stem cells provide a promising platform to recapitulate histological features of the human brain and model neural disorders. However, unlike animal models, brain organoids lack a reproducible topographic organization, which limits their application in modeling intricate biology, such as the interaction between different brain regions. To overcome these drawbacks, brain organoids have been pre-patterned into specific brain regions and fused to form an assembloid that represents reproducible models recapitulating more complex biological processes of human brain development and neurological diseases. This approach has been applied to model interneuron migration, neuronal projections, tumor invasion, oligodendrogenesis, forebrain axis establishment, and brain vascularization. In this review article, we will summarize the usage of this technology to understand the fundamental biology underpinning human brain development and disorders.