The multiple requirements of Jnk signaling during epidermal development

The epidermis is the biggest vertebrate organ that connects organisms to their environment: it keeps homeostasis by preventing infections, regulating temperature and adapting the organism to the external changes. Loss of skin integrity results various epithelial disorders giving rise to diseases like psoriasis or skin cancer, the most common form of cancer in the US. Jnk is one of the many signals required for epidermal development. It is a member of the MAPK (mitogen-activated protein kinase) family that regulates a wide range of biological processes from apoptosis, cell division, migration to homeostasis. However, it is currently unclear what processes Jnk signals regulate during epidermal development. Therefore, we have investigated extensively the processes regulated by Jnk during epidermal development. Active Jnk is present in the epidermis and in actively dividing cells throughout the embryo. Inhibiting JNK signaling by using morpholino (JNK1-MO) and pharmacological (SP600125) approaches results in embryonic mouth and many different developmental defects including epidermal defects derived from several problems in the embryo. First, we uncovered that Jnk inhibition leads to a major decrease in mitotic cells and an increase in apoptosis. Second, we determined that embryos with abnormal Jnk function have increased cellular stress demonstrated by the increase of a marker of cell detoxification. Finally we found that decreased Jnk signals modify cell adhesion: cell dissociation is delayed in EGTA treatment and E-Cadherins and actin accumulate at the membranes. Nevertheless, Jnk inhibition doesn’t significantly affect epidermal morphogenesis nor differentiation as all different cell types are identified in epithelial transplants. In conclusion we propose that JNK signals are necessary for maintained cell division and survival and may be necessary for modulating adhesion levels during epidermal cell movements.