Correlative fluorescence and transmission electron microscopy in tissues

Correlative microscopy has meant different things over the years; currently, this term refers to imaging the same exact structures with two or more imaging modalities. This commonly involves combining fluorescence and electron microscopy. Much of the recent work related to correlative microscopy has been done using cell culture models. However, many biological questions cannot be addressed in these models, but require instead the 3-dimensional organization of cells found in tissues. Herein, we discuss some of the issues related to correlative microscopy of tissues including the major reporter systems presently available for correlative microscopy. We present data from our own work in which we have focused on the use of ultrathin cryosections of tissues as the substrate for immunolabeling to combine immunofluorescence and electron microscopy of the same sub-cellular structures.