HIFs are heterodimeric transcription factors which have two structurally related subunits, an Orbifloxacin oxygen sensitive HIFa subunit and a constitutively expressed HIF? or ARNT subunit. Sox2 is important for pulmonary branching morphogenesis, epithelial cell differentiation and is exclusively expressed in the proximal parts of the lung. However, in mycHIF3a expressing lungs, Sox2 is present in epithelial cells of both proximal airways and certain alveoli at postnatal day 1, suggesting that Hif3a is able to induce proximal cell fate. The basal cell marker p63 is expressed in the esophagal and tracheal epithelium, and previously we showed that ectopic Sox2 expression induced the appearance of p63 positive cells in the epithelium of the bronchioles and Folinic acid calcium salt pentahydrate enlarged distal airspaces. Therefore, we analysed 
the distribution of basal cells in the mycHIF3a expressing lungs and found that p63 is abnormally expressed in the alveolar epithelial cells of mycHIF3a expressing lungs, contrasting the unique expression in the trachea. Hypoxia inducible factors are an important family of proteins involved in the regulation of the cellular response to hypoxia. Its functions are required from the earliest steps of mammalian life to the correct development of multiple organs and tissues, like the placenta, trophoblast formation, bone development, heart and vascular development. The importance of the hypoxia response was shown by the identification of human mutations in the VHL-HIF pathway in different diseases. Gene ablation studies in mice have revealed in more detail the specific and important roles of the different subunits of the Hifa/Hif? heterodimers. Inactivation of the stable subunit, Hif1?, resulted in severe embryonic defects and premature death. The disruption of the different Hifa genes identified specific roles for the individual Hifa isoforms. Hif1a knockout mice die early at gestation, have multiple developmental defects in neural tubeforrmation, vascularization, heart development, neural crest migration, whereas depending on the genetic background of the mouse strain, Hif2a knockout out mice ranging from early embryonic lethality to adulthood. Early-life stressors such as maternal undernutrition, overnutrition, hypercholesterolemia, corticosteroid therapy, uteroplacental insufficiency, or hypoxia program metabolic adaptations that initially favor survival but are ultimately detrimental to adult health. In laboratory rodents, low-protein diet during gestation and lactation has been known to reduce the life expectancy of offspring. The maternal protein restriction in the rat model of In Utero Protein Restriction is one of the most extensively explored model. The low-protein fed mothers give birth to growth-restricted offspring,, and when suckled by their mothers maintained on the same low-protein diet, they remain permanently growth-restricted, despite being weaned on a normal diet. Also, early-life undernutrition is associated with higher blood tryptophan levels, brain serotonin and impairment of the serotonergic control of feeding in female adult rats. Recently, we have shown that circadian clock of the hypothalamus is altered in young rats subsequently to perinatal undernutrition, however there is no proof that this dysregulation exists in other tissues as well. In rodents, the emergence of circadian clock outputs occur during the first 2 or 3 weeks after birth.