In recent years, Drosophila melanogaster has emerged as a powerful model for neuronal circuit development, pathology, and function. A major impediment to these studies has been the lack of a genetically encoded, specific, universal, and phenotypically neutral marker of the somatodendritic compartment. We have developed such a marker and show that it is effective and specific in all neuronal populations tested in the peripheral and central nervous system. The marker, which we name DenMark (Dendritic Marker), is a hybrid protein of the mouse protein ICAM5/Telencephalin and the red fluorescent protein mCherry. We show that DenMark is a powerful tool for revealing novel aspects of the neuroanatomy of developing dendrites, identifying previously unknown dendritic arbors, and elucidating neuronal connectivity.T o discover neuronal circuit architecture, genetic tools that specifically mark the pre-and postsynaptic cells and compartments are necessary. Drosophila is a leading genetic model organism in this regard; however, most neuronal circuits remain unmapped. Of particular note is the lack of a universal, phenotypically neutral, and specific marker of the somatodendritic and postsynaptic compartments. Several molecular differences between dendrites and axons, including the presence of different membrane and cytoskeletal proteins in neuronal subregions, have been identified (1, 2). Drosophila neurons exhibit the major kinds of compartmentalization present in mammalian neurons and the fly has emerged as a powerful system to study the establishment and maintenance of neuronal connections (3, 4). Almost all studies of neuronal circuits in the fly have relied on genetic markers such as CD8::GFP that outline the morphology of entire cells rather than particular subcellular compartments (5), as well as presynaptic markers such as Synaptotagmin, Synaptobrevin, and Bruchpilot GFP fusion proteins (6-11). However, more accurate identification and mapping of novel neuronal circuits has been hampered by the lack of a genetically encoded and phenotypically neutral dendritic marker. Over the years, many such markers have been proposed and several were recently examined (12), namely MAP2 (13, 14), Nod::YFP (4, 15-18), Homer::GFP (19), and DSCAM17.1::GFP (20, 21). The analysis of these markers reveals that none of them labels the entire somatodendritic field. Furthermore, it remains unclear whether the markers tested are neutral with respect to dendritic morphology.Intercellular adhesion molecules (ICAMs) mediate neuronal migration, axon elongation, and fasciculation, synaptogenesis, and synaptic plasticity (22). ICAM5, or Telencephalin, is a 130-kDa type I transmembrane glycoprotein comprising a characteristic extracellular domain, a single transmembrane region, and a short cytoplasmic region (23). The expression of ICAM5 is restricted to the mammalian brain telencephalon (24) but there is no homolog in invertebrates and lower vertebrates. The developmental appearance of ICAM5 parallels the time of dendritic elongation, branching, a...