Our study suggests that PTF, besides increasing robustness in cellular clocks, could be more directly and deeply involved in the production of oscillations than at first thought. Further research is necessary to elucidate the presence and the role of this genetic oscillator in natural cellular clocks. On the other hand, thanks to its simplicity, this model has the potential to be a new tool for engineering synthetic genetic oscillators. In this case the period and amplitude of the oscillations could be possibly controlled by externally manipulating the entry rate of the repressor molecules. The semaphorins are a family of evolutionarily conserved secreted and transmembrane proteins that participate in diverse biological processes, including central and peripheral nervous system development and regeneration, cardiovascular, renal and olfactory morphogenesis, immune system function, and cancer progression. Class 3 semaphorins comprise a subfamily of 7 secreted proteins best characterized as chemorepellants for growing neurons and axons. More recently it has been recognized that semaphorin 3 family members participate in a wide range of neuronal and non-neuronal processes in addition to the cytoskeletal remodeling involved in axonal pathfinding. Semaphorin 3A was the first identified vertebrate semaphorin, and has been extensively studied as a repulsive axon guidance cue. Sema3A also influences cortical dendritic morphology and neuronal migration, as well as apoptosis and proliferation of multiple cell types. Most of the neuronal effects of Sema3A are transduced by a holoreceptor complex, in which an obligatory co-receptor, neuropilin-1, functions as the ligand-binding subunit, and signaling occurs through activation of class A plexin receptor family members. Cell type-specific expression of different Sema3A receptor complexes is a key determinant of how this guidance cue exerts selective effects on cellular morphology. Both Sema3A and Nrp-1 are expressed in fetal, neonatal, and adult lung, yet data regarding how Sema3A signals influence lung morphology and function, or lung structural maintenance in response to LY2109761 abmole injury, are scant. Studies published several years ago suggested that Sema3A signaling through Nrp-1 attenuated branching morphogenesis of fetal lung explants maintained in culture. We recently demonstrated that cigarette smoke induced airspace enlargement and alveolar epithelial cell death is potentiated by conditional deletion of pulmonary epithelial Nrp-1 in the lungs of adult animals. These findings led us to hypothesize that Sema3A might be an essential mediator of distal airspace homeostasis. To test this hypothesis, we evaluated the distal lung morphology of mice with a targeted genetic deletion of Sema3A, maintained on a C57B/6 genetic background. This strain of mice was initially reported to show no significant embryonic or early postnatal mortality despite severe abnormalities in peripheral nerve projection, although Sema3A mice independently generated on the sv129 strain background died within a few days of birth.