Though the role of brain derived neurotrophic factor (BDNF) as a marker for major depressive disorder (MDD) and antidepressant efficacy has been widely studied, the role of BDNF in distinct groups of patients remains unclear. We evaluated the diagnostic value of BDNF as a marker of disease severity measured by HAM-D scores and antidepressants efficacy among MDD patients. Fifty-one patients who met DSM-IV criteria for MDD and were prescribed antidepressants and 38 controls participated in this study. BDNF in serum was measured at baseline, 1st, 2nd and 8th treatment weeks. Depression severity was evaluated using the Hamilton Rating Scale for Depression (HAM-D). BDNF polymorphism rs6265 (val66met) was genotyped. We found a positive correlation between blood BDNF levels and severity of depression only among untreated women with severe MDD (HAM-D>24). Serum BDNF levels were lower in untreated MDD patients compared to control group. Antidepressants increased serum BDNF levels and reduced between-group differences after two weeks of treatment. No correlations were observed between BDNF polymorphism, depression severity, duration of illness, age and BDNF serum levels. Further supporting the role of BDNF in the pathology and treatment of MDD, we suggest that it should not be used as a universal biomarker for diagnosis of MDD in the general population. However, it has diagnostic value for the assessment of disease progression and treatment efficacy in individual patients.

The nephron is the fundamental structural and functional unit of the kidney. Each mature nephron is patterned along a proximal-distal axis, with blood filtered at the proximal end and urine emerging from the distal end. In order to filter the blood and produce urine, specialized structures are formed at specific proximal-distal locations along the nephron, including the glomerulus at the proximal end, the tubule in the middle and the collecting duct at the distal end. The developmental processes that specify these different nephron segments are not fully understood. Wnt ligands, which are expressed in the nephric duct and later in the nascent nephron itself, are well-characterized inducers of nephrons, and are both required and sufficient for initiation of nephron formation from nephrogenic mesenchyme. Here, we present evidence that Wnt signaling also patterns the proximal-distal nephron axis. Using the chick mesonephros as a model system, a Wnt ligand was ectopically expressed in the coelomic lining, thereby introducing a source of Wnt signaling that is at right angles to the endogenous Wnt signal of the nephric duct. Under these conditions, the nephron axis was re-oriented, such that the glomerulus was always located at a position farthest from the Wnt sources. This re-orientation occurred within hours of exposure to ectopic Wnt signaling, and was accompanied initially by a repression of the early glomerular podocyte markers Wt1 and Pod1, followed by their re-emergence at a position distant from the Wnt signals. Activation of the Wnt signaling pathway in mesonephric explant cultures resulted in strong and specific repression of early and late glomerular markers. Finally, cytoplasmic β-catenin, indicative of active canonical Wnt signaling, was found to be enriched in the distal as compared with the proximal region of the forming nephron. Together, these data indicate that Wnt signaling patterns the proximal-distal axis of the nephron, with glomeruli differentiating in regions of lowest Wnt signaling.

Background: During the course of development, the vertebrate nephric duct (ND) extends and migrates from the place of its initial formation, adjacent to the anterior somites, until it inserts into the bladder or cloaca in the posterior region of the embryo. The molecular mechanisms that guide ND migration are poorly understood. Results: A novel Gata3-enhancer-Gfpbased chick embryo live imaging system was developed that permits documentation of ND migration at the individual cell level for the first time. FGF Receptors and FGF response genes are expressed in the ND, and FGF ligands are expressed in surrounding tissues. FGF receptor inhibition blocked nephric duct migration. Individual inhibitors of the Erk, p38, or Jnk pathways did not affect duct migration, but inhibition of all three pathways together did inhibit migration of the duct. A localized source of FGF8 placed adjacent to the nephric duct did not affect the duct migration path. Conclusions: FGF signaling acts as a "motor" that is required for duct migration, but other signals are needed to determine the directionality of the duct migration pathway. Developmental Dynamics 244:157-167, 2015. V C 2014 Wiley Periodicals, Inc.

Highlights d Convergence of the coelomic epithelium involves cell flattening and disorganization d Hh signaling regulates coelomic epithelium morphogenesis and N-cadherin distribution d Sec5 and RhoU function downstream of Hh d Hh signaling controls dorsal mesentery midline positioning