3D Neurovascular Unit Tissue Model to Assess Responses to Traumatic Brain Injury.

The neurovascular unit (NVU) is a critical interface in the central nervous system that links vascular interactions with glial and neural tissue. Disruption of the NVU has been linked to the onset and progression of neurodegenerative diseases. Despite its significance the NVU remains challenging to study in a physiologically relevant manner.

Microbes affect gut epithelial cell composition through immune-dependent regulation of intestinal stem cell differentiation.

Gut microbes play important roles in host physiology; however, the mechanisms underlying their impact remain poorly characterized. Here, we demonstrate that microbes not only influence gut physiology but also alter its epithelial composition. The microbiota and pathogens both influence intestinal stem cell (ISC) differentiation.

Multiscale analysis reveals that diet-dependent midgut plasticity emerges from alterations in both stem cell niche coupling and enterocyte size.

The gut is the primary interface between an animal and food, but how it adapts to qualitative dietary variation is poorly defined. We find that the midgut plastically resizes following changes in dietary composition. A panel of nutrients collectively promote gut growth, which sugar opposes.

Hippo, TGF-β, and Src-MAPK pathways regulate transcription of the upd3 cytokine in Drosophila enterocytes upon bacterial infection.

Cytokine signaling is responsible for coordinating conserved epithelial regeneration and immune responses in the digestive tract. In the Drosophila midgut, Upd3 is a major cytokine, which is induced in enterocytes (EC) and enteroblasts (EB) upon oral infection, and initiates intestinal stem cell (ISC) dependent tissue repair. To date, the genetic network directing upd3 transcription remains largely uncharacterized.

Regional Cell-Specific Transcriptome Mapping Reveals Regulatory Complexity in the Adult Drosophila Midgut.

Deciphering contributions of specific cell types to organ function is experimentally challenging. The Drosophila midgut is a dynamic organ with five morphologically and functionally distinct regions (R1-R5), each composed of multipotent intestinal stem cells (ISCs), progenitor enteroblasts (EBs), enteroendocrine cells (EEs), enterocytes (ECs), and visceral muscle (VM). To characterize cellular specialization and regional function in this organ, we generated RNA-sequencing transcriptomes of all five cell types isolated by FACS from each of the five regions, R1-R5.

Methods to assess intestinal stem cell activity in response to microbes in Drosophila melanogaster.

Drosophila melanogaster presents itself as a powerful model for studying the somatic stem cells of the gut and how bacteria affect intestinal homeostasis. The Gal4/UAS/Gal80 (ts) system allows for temporally controlled expression of fluorescent proteins, RNAi knock-down, and other genetic constructs targeted to specific cell populations in the midgut. Similarly, FLP/FRT-mediated somatic recombinations in intestinal stem cells (ISCs) are utilized to visualize and analyze the clonal lineages of individual or populations of stem cells.