What about early stages of immune cell type evolution? In general, among the invertebrate coelomocytes (cells floating in the coelom), granular hemocytes (granulocytes) are considered homologous to vertebrate adaptive immune cells [7 and 45]. Invertebrate

blood cells have been subclassified A-1210477 mouse by morphological criteria, but are widely viewed as stage- or organismal state-specific descendants of the same lineage [45]. In the light of the notion of three immune cell types at the base of the vertebrate lineage, it will be interesting to assess when this divergence occurred. The availability of extensive molecular and morphological fingerprint catalogues of human and mouse blood cell types [46 and 47] will enable high-resolution AT13387 comparisons with any cell-type specific transcriptomic data on the invertebrate side. The identification of cellular modules in the various animal genomes and the mapping of components constituting these modules on the animal tree, as exemplified for the vertebrate

stem line in Figure 1, provide an exiting new view of phenotypic evolution. With time, a comprehensive view on the modules present at specific nodes of the tree will emerge. In a pioneer study, Wenger and Galliot have recently identified four ‘hot spots’ of protein innovation on the evolutionary lineage leading to the vertebrates [48••]. Once the identified structural proteins that evolved during these innovation periods are fully Thiamet G understood and sorted into modules, this will result in a refined picture of the complexity of the respective ancestors. Yet, the power of comparative genomics in reconstructing the evolution of cellular modules and cell types necessarily faces its limits. In many cases, the mere presence of a protein in a given genome will not be sufficient to assign it to a specific cellular module (unless biochemical or other relevant data is already available). Also, in many cases the presence of a module will also not suffice to attribute

it to the diverse cell type(s) present in each animal. In most studies discussed here, this link has been (tentatively) established by wholemount in situ expression analysis of selected genes; for example, co-expression of the postsynaptic density module with the ‘neurogenic’ genes in the sponge Amphimedon reveals its presence in sensory cells [ 28 and 49]; or, although the genes for vertebrate Z-disk proteins alpha-actinin, muscleLIM and Ldb3 are present in cnidarians, they are not co-expressed in the striated muscle cells [ 14••], which indicates that the latter evolved convergently (see above). However, in some species hybridisation protocols are not available; and simultaneous co-labelling of animals with probes detecting transcripts of two or more genes is tedious and will be impossible in many cases. In this context, single cell transcriptomics provides an exciting new opportunity for unbiased and quantitative characterization of cell types [50].