The Merkel Cell Carcinoma Collaborative (MC3) Institute recently featured a Q&A with Biology Associate Professor Jeff Rasmussen about his lab's most recent Merkel cell paper published in Development. Excerpt from the article:
Jeff Rasmussen, PhD, a member of the MC3 Institute, leads a developmental biology lab at the University of Washington focused on skin development and regeneration. The lab uses zebrafish as a model due to its accessibility to in vivo imaging and genetic manipulation.
In a recent publication, Jeff and his team describe the discovery of a transitional cell type, dendritic Merkel cells (dMCs), that connects keratinocyte progenitors to mature touch-sensitive Merkel cells.
This work reveals how actin cytoskeletal remodeling and Ectodysplasin A signaling drive progenitors to adopt the specialized Merkel cell shape.
In the Q&A below, Jeff shares his thoughts on this study and his lab's ongoing work.
Why does this study matter?
The cellular and molecular mechanisms that give rise to Merkel cells have been of long-standing interest to developmental and sensory biologists. For example, ultrastructural studies in the 1970s identified “transitional cells” that displayed hybrid properties between basal stem cells and MCs, providing some of the first evidence that MCs derive from epidermal progenitors.
Later immunofluorescence-based studies identified cells stained by MC-specific antibodies (cytokeratins 18 and 20) but with distinct, dendritic morphologies. These “dendritic Merkel cells” (dMCs) have since been observed in several types of vertebrate skin, including human fetal skin. However, any clear connection between transitional cells, dMCs, and Merkel cells has remained unclear, but is highly relevant to understanding Merkel cell ontogeny.
Our manuscript directly addresses this knowledge gap using a combination of live imaging, molecular analysis and genetics. We found that zebrafish dMCs exhibit molecular properties of both basal stem cells and Merkel cells, leading us to propose that transitional cells and dMCs represent similar cellular intermediates. Surprisingly, in contrast to epithelial-like Merkel cells, dMCs exhibit mesenchymal-like behaviors and migrate locally within the epidermis before directly maturing into Merkel cells.
Lastly, we demonstrate that Ectodysplasin A signaling, a conserved regulator of skin development, is required for the proper morphologies of dMCs and Merkel cells. So our study is significant because it identifies the immediate precursors to Merkel cells and describes their cellular behaviors.
Read the full Q&A on the MC3 Institute website.