zebrafish skin in white, immune cells in cyan Immune cells depend on a dynamic cytoskeleton to perform functions such as directed migration and phagocytosis. While roles for the actin cytoskeleton in these functions has received much attention, the microtubule cytoskeleton remains relatively understudied. Moreover, how immune cells efficiently navigate confined epithelial tissues that present constraints to cell motility is not fully understood. To address these knowledge gaps, Dr. Eric Peterman and colleagues exploited our previously established model of visualizing and manipulating tissue-resident macrophages in adult zebrafish skin explants. Adult zebrafish skin offers many advantages to studying immune cell dynamics, including optical transparency and the ability to apply pharmacological agents to manipulate the cytoskeleton. Langerhans cells are tissue-resident macrophages that extend long, dynamic dendrites between keratinocytes to surveil the epidermis. Langerhans cells promote wound healing in murine models, and our lab previously found that Langerhans cell migration and phagocytosis of debris require actin dynamics.

To examine the requirements of microtubules in tissue damage responses, we combined our skin explant model with tools to visualize and perturb microtubules in Langerhans cells. Within our manuscript, we acutely stabilized or depolymerized the microtubule cytoskeleton, providing insights into microtubule requirements during steady-state conditions and the responses to tissue damage. We present data supporting non-mutually exclusive roles for microtubules in regulating ROCK-dependent actin dynamics and cell steering around keratinocyte obstacles during directional cell migration. Altogether, our data support multiple roles for microtubules in the behaviors of tissue-resident macrophages operating within a confined microenvironment and define adult zebrafish epidermis as a powerful model to study microtubule dynamics of immune cells within an epithelium.

Read the preprint here!

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