Hippo signaling controls cellular processes that ultimately impact organogenesis and homeostasis. Consequently, disease states including cancer can emerge when signaling is deregulated. The major pathway transducers Yap and Taz require cofactors to impart transcriptional control over target genes. Research into Yap/Taz-mediated epigenetic modifications has revealed their association with chromatin-remodeling complex proteins as a means of altering chromatin structure, therefore affecting accessibility and activity of target genes. Specifically, Yap/Taz have been found to associate with factors of the GAGA, Ncoa6, Mediator, Switch/sucrose nonfermentable (SWI/SNF), and Nucleosome Remodeling and Deacetylase (NuRD) chromatin-remodeling complexes to alter the accessibility of target genes. This review highlights the different mechanisms by which Yap/Taz collaborate with other factors to modify DNA packing at specific loci to either activate or repress target gene transcription.
The chemokine CXCL12 has important functions in immune and central nervous systems. Moreover, a global disruption of CXCL12 in mice results in perinatal lethality. To circumvent this impediment and provide a tool for analyzing CXCL12 functions in specific organ systems, we have generated a mouse line harboring a loxP-site flanked exon 2 of CXCL12. A germ line deleter, bactin::cre was used to remove a CXCL12 exon 2 and subsequently systemic CXCL12 exon 2 deficient embryos were generated. These mutant embryos showed a marked depletion of CXCL12 transcript. As expected from the global mutant phenotype, our mutants were also characterized by highly irregular cerebellar cytoarchitecture of the external granule layer as well as altered radial migration of midbrain dopaminergic neurons. Importantly, migration of the pontine grey nucleus (PGN) was derailed and remarkably resembled the global mutant phenotype of the CXCL12 receptor -CXCR4 in this system. Despite the fact that CXCL12 signaling can be mediated through receptors other than CXCR4, our results indicate a monogamous relationship between the CXCL12 ligand and CXCR4 receptor in controlling PGN migration. Our findings further expand on the understanding of CXCL12 function in PGN development. Moreover, phenotypic similarities between our mutants and mice harboring a global CXCL12 disruption support the validity of our line. Importantly, these results strongly suggest that our conditional CXCL12 line can be used as a powerful tool to manipulate CXCL12 signaling and function in vivo.
The global pandemic of coronavirus disease has significantly impacted medical education, including removing trainees from clinical environments, transitioning didactic sessions to virtual platforms, and necessitating creative solutions to provide interactive learning opportunities in a virtual, socially distant setting. Human gross anatomy education, with its emphasis on hands‐on, team‐based, active learning by body donor dissection, has been particularly impacted by these transitions. Dissection is considered the best practice for learning gross anatomy and has been shown to enhance learning over non‐dissection‐based methods. At the Medical College of Wisconsin, team‐based, body donor dissections are the basis for the Clinical Human Anatomy course. However, the pandemic necessitated changes to the format of laboratory activities. For the 2020‐2021 academic year, students either completed anatomy labs in‐person in a socially distant environment or virtually. This provided an opportunity to directly compare the effect of different laboratory instructional modalities on student performance within a single course. All first‐year medical students were enrolled in the same Clinical Human Anatomy course, attended identical didactic sessions, and were assessed by identical examinations that included lecture‐based questions as well as laboratory image‐based questions. As the semester progressed and coronavirus disease case numbers rose, students were offered two options for completing laboratory instruction: (1) continue dissections in socially distant pairs or (2) transition to a virtual lab format. The virtual lab format included a self‐directed module which guided students through the dissections they would have done in person. Each module consisted of a PowerPoint presentation that incorporated interactive software (3D4Medical Complete Anatomy) and dissection images. The self‐directed modules were followed by interactive Zoom sessions, wherein faculty reviewed a prosection and posed clinically relevant questions to the meeting attendees. Students who opted for the virtual lab format were able to review dissections in‐person on their own time or with a tutor. Likewise, students who opted to continue dissection had access to the virtual modules and recordings of the Zoom sessions. Comparison between students completing labs virtually or in‐person showed no difference in aggregate performance on examinations. This study examined medical knowledge and did not investigate other competencies impacted by lab activities (teamwork, dealing with death, and the “first patient” experience). We consider hands‐on dissection to be the gold‐standard format for learning gross anatomy, but this study showed by direct comparison in a single course, that multiple laboratory formats can yield equivalent understanding of the complex structure of the body.
Community outreach is an institutional mission at the Medical College of Wisconsin (MCW); which has three campuses spread throughout Wisconsin. There are numerous outreach programs established at each location run by medical students. These outreach programs are largely targeted at middle and high school‐aged students, focusing on promoting physical wellness and fostering an interest in healthcare‐related careers. Extension of these programs to underserved students who may not be able to travel to an MCW site is of particular interest. Although each MCW campus has plastic anatomical models and fixed anatomical specimens set aside for these programs, both have hindrances for use in community education. Plastic anatomical models are a step removed from actual specimens, and do not fully represent the potential for anatomical variations. Although most engaging, wet formalin‐fixed specimens can be irritating to the eyes and respiratory system and must be handled in a well‐ventilated environment. Using funding from the Medical College of Wisconsin and the American Association for Anatomy (AAA), we created a small library of plastinated organs to use during community outreach programs. The plastination process consists of initial organ fixation followed by dehydration of the organ in acetone. Following dehydration, polymer is infused into the organ via vacuum‐pressure and the organ is ultimately cured using gas or UV‐light. These organs are odorless, non‐toxic hardened tissue specimens that do not decay and can be easily transported and handled freely at both on and off‐campus environments. For this project, 3 hearts, 3 kidneys, and 3 brains were harvested from body donors enrolled in MCW’s Anatomical Gift Registry program. These organs were plastinated and sectioned to highlight internal and external anatomical features. Plastination kits consisting of a heart, kidney, and brain (along with educational pamphlets describing relevant anatomy of each organ) were distributed to each campus. Following interaction with plastinated organs, program participants are asked to complete a survey about their learning and interactions with these specimens. All research involving human subjects undergoes strict review by MCW’s IRB. Since their recent implementation, these programs have reached 201 community students and are ongoing throughout the year at all campus locations. We are currently collecting and analyzing user perception surveys, evaluating what students learned during their interactions with the plastinated organs and their preferences for using plastinated vs. wet‐fixed specimens. Preliminary feedback has been positive, where MCW medical students have expressed these plastinates provide a beneficial resource for community outreach programs. Support or Funding Information Funding for this project was obtained through the following sources: AAA ‐ Education Outreach Grant and MCW Dean’s Programmatic Dollars.
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