Using Developmental Paradigms To Engineer Complex Human Stomach Tissue from Stem Cells
During fetal development, organs of the gastrointestinal tract form from cells of the three embryonic germ layers; the endoderm, mesoderm and ectoderm. MDB student Alexandra Eicher from the Wells lab separately generated foregut endoderm, splanchnic mesoderm, and ectodermal neural crest cells from human pluripotent stem cell and combined them in a petri dish to make stomach organoids. Following a month of self-assembly in vitro, the tissue grew and differentiated when transplanted into immunocompromised mice. This resulted in gastric tissues morphologically indistinguishable from a perinatal human stomach with glandular epithelium and functionally innervated smooth muscle capable of gastric contractions. This work, published in Cell Stem Cell, represents a major advance in the field of regenerative medicine and may one day lead to approaches to replace stomach tissue in patients. Read more in the CCRF science blog.How Cell Polarity Controls Placenta Formation For Successful Pregnancy
The Dey lab in the Reproductive Sciences Center discovered an unexpected connection between cannabinoid receptors and pregnancy. Directed trophoblast migration toward the maternal mesometrial pole is critical for placentation and pregnancy success. Kim et al., reports in the Proceedings of the National Academy of Sciences that the Cannabinoid Receptor 1 intersecting with the planar cell polarity protein VANGL2, is indispensable to enable directed migration and invasion of trophoblast cells into the maternal tissue during placenta formation. This study points to the need for further studies on the potential impact of cannabinoid use on pregnancy.Understanding The Cell Signaling Pathways and Transcriptional Programs Of Organ Development
Heart and lung development must have careful coordination for proper cardiopulmonary function by the time a newborn takes its first breath. Disruption in the genetic programs that control this can result in devastating and often lethal congenital anomalies. Using frog embryos as a model of human development, Rankin et al. from the Zorn lab report in eLife the molecular cascade downstream of the transcription factor Tbx5 that orchestrates cardiopulmonary development.Notch (N) receptors convert cell-to-cell contact with ligands into changes in gene expression via association with a DNA binding partner, CSL. Utilizing Notch signaling during the development of most organs activates target genes regulated by both cooperative and non-cooperative DNA sites.
The utilization of Notch signaling during the development of most organs activates target genes regulated by both cooperative and non-cooperative DNA sites. Notch (N) receptors convert cell-to-cell contact with ligands into changes in gene expression via association with a DNA binding partner, CSL. CSL can either bind Notch or an antagonistic repressor (Hairless, H). A collaborative study led by the Gebelein lab shows that the CSL/N activation complexes preferentially bind Notch target genes with cooperative sites over the CSL/H complex. In contrast, non-cooperative sites are bound equally by both complexes. Thus, Notch target genes rich with cooperative sites are relatively insensitive to changes in co-repressor levels.
The Campbell lab led another collaborative effort seeking insights into how the cerebral cortex connects to the brainstem and spinal cord via the internal capsule, a bundle of axon tracts that also carry reciprocal connections between the cerebral cortex and thalamus in the anterior end. While it is well known that these cortical and thalamic axons rely on each other to reach their targets correctly, less known is how cortical axons traverse the brain to reach the brainstem and spinal cord. Ehrman et al. demonstrate that basal ganglia-derived striatonigral axons, which pioneer the internal capsule, serve as essential substrates for these cortical axons to correctly navigate through the brain.
