Investigating the Regulation of Desmosomes During Mouse Hair Follicle Morphogenesis

Abstract

Convergent extension, or the simultaneous shortening and elongation of tissue along orthogonal axes, is a process that regularly occurs during embryogenesis. Convergent extension has been predominantly studied in Drosophila, where it was discovered that the underlying mechanism behind the process in epithelial cells is cell intercalation, or the exchanging of neighboring cells. Currently, the leading model to describe cell intercalation centers on the rearrangement of cell-cell junctions called adherens junctions. However, there are other types of junctions that exist that the current leading model does not address. For example, unlike in the Drosophila, the mammalian epidermis is rich with another type of cell junction: desmosomes. Desmosomes link the intermediate filament cytoskeleton of adjacent cells. They enable the epidermis to withstand mechanical forces and serve as particularly strong adhesion between cells. Considering their particularly “sticky” nature, hypothetically, how would desmosomes remodel during cell intercalation in mammalian skin epithelial cells? Here, I report the findings of my project investigating how desmosome remodeling occurs during cell rearrangement. A specific process in mammalian skin development I am studying to further understand desmosome remodeling during cell rearrangement is hair follicle morphogenesis. Hair follicles develop from hair placodes, clusters of epithelial cells that arise from an initially undifferentiated epidermis. After forming, hair placodes bud downward into the dermis and later become polarized through cell intercalation so that they point and grow in an anterior direction. Whole-mount immunostaining and correlating fluorescence intensity heat maps showed that expression of desmosomal proteins desmoplakin and plakoglobin are lower in the hair placode relative to unspecified interfollicular cells. Subsequently, I investigated whether or not planar cell polarity (PCP), a developmental cue that sparks hair placode cell rearrangement, was the trigger for desmosome remodeling. Whole-mount immunostaining and correlating fluorescence intensity heat maps looking at both wild type and PCP mutant skin showed that expression of desmosomal proteins desmoplakin and plakoglobin remained lower in the hair placode relative to unspecified interfollicular cells. Taken all together, this data suggested that decreased desmosomal proteins in hair placodes allow for hair placode cell movement to occur. PCP, however, is not a developmental cue that triggers desmosome remodeling. In the future, one should characterize the expression of other desmosomal proteins and their localization. Other possible developmental cues, such as the the Wnt/Beta-catenin pathway and the Shh signaling pathway, should also be explored to see if they trigger desmosomal remodeling.