miR-205: A Multifaceted microRNA Essential for Lacrimal Gland Development
While microRNAs are critical in various organs during development, their roles during ectodermal appendage development remain underappreciated. This body of work encompasses research focused on a microRNA, miR-205, which is enriched in the skin and several ectodermal appendages, including teeth, hair follicles, and various glands. We have identified miR-205 as an essential microRNA for murine postnatal survival. By postnatal day 7, 50% of knockout mice were runted and these mice died by postnatal day 14. Knockout animals developed prominent skin defects that emerged postnatally. However, the skin barrier function remained intact. In addition, we uncovered an embryonic phenotype in an important ocular supporting gland known as the lacrimal gland, a gland we profiled extensively. Indeed, we uncovered novel features of epithelial cell lineage commitment and identified progenitors pools in the adult lacrimal. When we deleted miR-205, More than 70% of lacrimal glands were missing. By evaluating lacrimal development in control and knockout mice, we revealed that miR-205 is required for early lacrimal gland development, and specifically lacrimal gland initiation. Mechanistic investigation uncovered several miR-205 targets, including Inppl1 and Cadm1, known negative regulators of Akt signaling. Furthermore, we demonstrated that Akt signaling is activated downstream of Fgf10, the established inducer of lacrimal gland development. Combinatorial deletion of miR-205 and Fgf10 completely inhibited lacrimal initiation in 100% of mice, suggesting a possible genetic interaction between the two genes. Together, these data illustrate the important roles of miR-205 during embryonic and postnatal development. Furthermore, this work uncovered a variety of new, relevant, and important information about lacrimal gland development and the role of microRNAs during murine development.