PDK1 Is a Regulator of Epidermal Differentiation that Activates and Organizes Asymmetric Cell Division | Zendy

Teruki Dainichi | Zendy; Matthew S. Hayden | Zendy; SungGyoo Park | Zendy; Hyun-Ju Oh | Zendy; John J. Seeley | Zendy; Yenkel GrinbergBleyer | Zendy; Kristen M. Beck | Zendy; Yoshiki Miyachi | Zendy; Kenji Kabashima | Zendy; Takashi Hashimoto | Zendy; Sankar Ghosh | Zendy

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PDK1 Is a Regulator of Epidermal Differentiation that Activates and Organizes Asymmetric Cell Division

Author(s) -

Teruki Dainichi,

Matthew S. Hayden,

SungGyoo Park,

Hyun-Ju Oh,

John J. Seeley,

Yenkel GrinbergBleyer,

Kristen M. Beck,

Yoshiki Miyachi,

Kenji Kabashima,

Takashi Hashimoto,

Sankar Ghosh

Publication year - 2016

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2016.04.051

Subject(s) - microbiology and biotechnology , hairless , notch signaling pathway , epidermis (zoology) , conditional gene knockout , biology , cellular differentiation , activator (genetics) , protein kinase b , cell division , signal transduction , cell , phenotype , anatomy , genetics , gene

Asymmetric cell division (ACD) in a perpendicular orientation promotes cell differentiation and organizes the stratified epithelium. However, the upstream cues regulating ACD have not been identified. Here, we report that phosphoinositide-dependent kinase 1 (PDK1) plays a critical role in establishing ACD in the epithelium. Production of phosphatidyl inositol triphosphate (PIP3) is localized to the apical side of basal cells. Asymmetric recruitment of atypical protein kinase C (aPKC) and partitioning defective (PAR) 3 is impaired in PDK1 conditional knockout (CKO) epidermis. PDK1(CKO) keratinocytes do not undergo calcium-induced activation of aPKC or IGF1-induced activation of AKT and fail to differentiate. PDK1(CKO) epidermis shows decreased expression of Notch, a downstream effector of ACD, and restoration of Notch rescues defective expression of differentiation-induced Notch targets in vitro. We therefore propose that PDK1 signaling regulates the basal-to-suprabasal switch in developing epidermis by acting as both an activator and organizer of ACD and the Notch-dependent differentiation program.

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