Impaired Hair Follicle Morphogenesis and Polarized Keratinocyte Movement upon Conditional Inactivation of Integrin-linked Kinase in the Epidermis

• DOI: 10.1091/mbc.e07-06-0526
• Publication Date: 2008-01-31T01:53:57Z
• Authors: Kerry-Ann Nakrieko; Ian Welch; Holly Dupuis; Dawn Bryce; Agnieszka Pajak; René St. Arnaud; Shoukat Dedhar; Sudhir J. A. D'Souza; Lina Dagnino
• Keywords: Integrin-linked kinase; Epidermis (zoology); Cell polarity

Integrin-linked kinase (ILK) is key for cell survival, migration, and adhesion, but little known about its role in epidermal development homeostasis vivo. We generated mice with conditional inactivation of the Ilk gene squamous epithelia. These die perinatally exhibit skin blistering severe defects hair follicle morphogenesis, including greatly reduced numbers, failure to progress beyond very early developmental stages, pronounced follicular keratinocyte proliferation. ILK-deficient epidermis shows abnormalities adhesion basement membrane differentiation. cultured keratinocytes fail attach spread efficiently multiple actin cytoskeletal organization. causes impaired ability form stable lamellipodia, directionally migrate, polarize. are accompanied by abnormal distribution active Cdc42 protrusions, as well activation Rac1 upon induction migration scraped monolayers. Significantly, alterations spreading forward movement single cells can be rescued expression constitutively or RhoG. Our studies underscore a central distinct ILK polarized movements, two aspects epithelial morphogenesis function.