Germ layer formation and primary axis development rely on Fibroblast growth factors (FGFs). In Xenopus, the secreted serine protease HtrA1 induces mesoderm and posterior trunk/tail structures by facilitating the spread of FGF signals. Here, we show that the serpin Protease nexin-1 (PN1) is transcriptionally activated by FGF signals, suppresses mesoderm and promotes head development in mRNAinjected embryos. An antisense morpholino oligonucleotide against PN1 has the opposite effect and inhibits ectodermal fate. However, ectoderm and anterior head structures can be restored in PN1-depleted embryos when HtrA1 and FGF receptor activities are diminished, indicating that FGF signals negatively regulate their formation. We show that PN1 binds to and inhibits HtrA1, prevents degradation of the proteoglycan Syndecan 4 and restricts paracrine FGF/Erk signaling. Our data suggest that PN1 is a negative-feedback regulator of FGF signaling and has important roles in ectoderm and head development.

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Adult neural stem/precursor cells (NSPCs) residing in the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus are involved in the memory formations and psychological problems. It is believed that basal levels of glucocorticoids are essential for neuronal development, plasticity, and survival, while stress-mediated levels of glucocorticoids produce neuronal loss. Degeneration of NSPCs by the apoptotic and necrotic stimuli have great devastating outcomes on the brain and contributes to the pathophysiology of neurological as well as psychological disorders. Using MTT assay, acridine orange, and TUNEL assay, we have demonstrated that cortisol at high and excessive (more than 5 μM) levels had anti-proliferative effects on the NSPCs derived from subventricular and subgranular zones in a dose- and time-dependent manner through apoptosis as well as necrosis. These outcomes can highlight the role of stress-mediated decline of adult neurogenesis in the aging brain and interconnect stress-mediated cortisol secretion with brain aging diseases.

The role of paraxial mesoderm or the somites in decision of ectoderm to acquire the neuroepithelial fate and its subsequent diversification to functional neural subtypes especially in mammalians is obscure. Here we report, for the first time, the influence of the co-culture of alginate bead-encapsulated somites isolated from chick embryos on neural differentiation in mouse embryonic stem cells-derived embryoid bodies (EBs). Using a combination of morphology, immunofluorescence, flow cytometry, semiquantitative, and conventional RT-PCR techniques, we show that the somites induce rosette structures and weakly enhance neural differentiation and neural markers in a dose-dependent manner in comparison to the control group, but its effect is lower than retinoic acid treatment of EBs. By liquid chromatography-mass spectrometry, it was revealed that somitic cells synthesized and released retinoids into the medium. However, no effective influence of somitic co-culture on rostrocaudal or dorsoventral patterning is seen. Therefore, like amphibians, somites have a modest neural-inducing activity in amniotes.