Insulin/IGF-1 Controls Epidermal Morphogenesis via Regulation of FoxO-Mediated p63 Inhibition

• DOI: 10.1016/j.devcel.2013.05.017
• Publication Date: 2013-07-29T22:18:58Z
• Authors: Christian Günschmann; Heike Stachelscheid; Mehmet Deniz Akyüz; Annika Schmitz; Caterina Missero; Jens C. Brüning; Carien M. Niessen
• Keywords: Epidermis (zoology); Transcription

The multilayered epidermis is established through a stratification program, which accompanied by shift from symmetric toward asymmetric divisions (ACD), process under tight control of the transcription factor p63. However, physiological signals regulating p63 activity in epidermal morphogenesis remain ill defined. Here, we reveal role for insulin/IGF-1 signaling (IIS) regulation activity. Loss IIS leads to biased loss ACD, resulting impaired stratification. Upon IIS, FoxO factors are retained nucleus, where they bind and inhibit p63-regulated transcription. This reversed small interfering RNA-mediated knockdown FoxOs. Accordingly, transgenic expression constitutive nuclear variant abrogates ACD inhibits Collectively, present study reveals critical IIS-dependent coordination during epithelial morphogenesis.