Netrin Signaling Defines the Regional Border in the Drosophila Visual Center

Summary: The brain consists of distinct domains defined by sharp borders. So far, the mechanisms of compartmentalization of developing tissues include cell adhesion, cell repulsion, and cortical tension. These mechanisms are tightly related to molecular machineries at the cell membrane. However, we and others demonstrated that Slit, a chemorepellent, is required to establish the borders in the fly brain. Here, we demonstrate that Netrin, a classic guidance molecule, is also involved in the compartmental subdivision in the fly brain. In Netrin mutants, many cells are intermingled with cells from the adjacent ganglia penetrating the ganglion borders, resulting in disorganized compartmental subdivisions. How do these guidance molecules regulate the compartmentalization? Our mathematical model demonstrates that a simple combination of known guidance properties of Slit and Netrin is sufficient to explain their roles in boundary formation. Our results suggest that Netrin indeed regulates boundary formation in combination with Slit in vivo. : Neuroscience; Developmental Neuroscience; Mathematical Biosciences Subject Areas: Neuroscience, Developmental Neuroscience, Mathematical Bioscience

Pathophysiology of Lung Injury Induced by Common Bile Duct Ligation in Mice

<div><p>Background</p><p>Liver dysfunction and cirrhosis affect vasculature in several organ systems and cause impairment of organ functions, thereby increasing morbidity and mortality. Establishment of a mouse model of hepatopulmonary syndrome (HPS) would provide greater insights into the genetic basis of the disease. Our objectives were to establish a mouse model of lung injury after common bile duct ligation (CBDL) and to investigate pulmonary pathogenesis for application in future therapeutic approaches.</p><p>Methods</p><p>Eight-week-old Balb/c mice were subjected to CBDL. Immunohistochemical analyses and real-time quantitative reverse transcriptional polymerase chain reaction were performed on pulmonary tissues. The presence of HPS markers was detected by western blot and microarray analyses.</p><p>Results</p><p>We observed extensive proliferation of CD31-positive pulmonary vascular endothelial cells at 2 weeks after CBDL and identified 10 upregulated and 9 down-regulated proteins that were associated with angiogenesis. TNF-α and MMP-9 were highly expressed at 3 weeks after CBDL and were less expressed in the lungs of the control group.</p><p>Conclusions</p><p>We constructed a mouse lung injury model by using CBDL. Contrary to our expectation, lung pathology in our mouse model exhibited differences from that of rat models, and the mechanisms responsible for these differences are unknown. This phenomenon may be explained by contrasting processes related to TNF induction of angiogenic signaling pathways in the inflammatory phase. Thus, we suggest that our mouse model can be applied to pulmonary pathological analyses in the inflammatory phase, i.e., to systemic inflammatory response syndrome, acute lung injury, and multiple organ dysfunction syndrome.</p></div

Protein array analysis of serum from common bile duct ligated (CBDL) and sham operated mice.

<p>Mean pixel density of representative proteins analyzed by protein array in serum isolated from CBDL and sham operated mice.</p

Immunofluorescent localization of von Willebrand factor (vWF) and tumor necrosis factor alpha (TNF-α).

<p>Representative images of lung tissues isolated 3 weeks after the CBDL or sham procedures showing vWF (red), TNF-α (green), and DAPI, nuclear staining marker (blue). (a–c) Staining at 3 weeks after the CBDL and (d–f) sham procedures. TNF-α was more highly expressed in pulmonary endothelial vascular cells at 3 weeks after CBDL than those of the sham operated group (original magnification, ×20).</p