Followed by the onset of cone photoreceptor and horizontal cell genesis

Lineage analyses in several species have shown that these cell types are produced from a pool of multipotent progenitor cells throughout development, with even terminal divisions capable of giving rise to two very different cell types, such as a photoreceptor cell and an interneuron. -thymidine based birthdating studies have demonstrated that these retinal cell types are generated in overlapping intervals and with a conserved birth order. The major output neuron, the retinal ganglion cell, is the first to be generated, followed by the onset of cone photoreceptor and horizontal cell genesis shortly thereafter. The appearance of another type of interneuron, the amacrine cell, occurs slightly later still,Lucidenic-acid-B with rod photoreceptor cells, bipolar cells and Muller glia being the latest born retinal cell types, Kru¨ppel, Pdm and Castor. Experiments in which the expression of Hb was maintained beyond its normal window resulted in an extension of the early competence state and a corresponding increase in the number of early born neurons generated. When this enforced expression of Hb was removed, neuroblasts expressed Kr and continued on to the later competence states. The genes that define the particular RPC competence states as well as those that regulate the transitions between them are only just beginning to be identified. Large scale gene expression profiling studies have been utilized as a first step toward revealing all of the potential transcripts involved in RPC biology. However, previous microarray and SAGE based screening studies focused on the entire retina, thus homogenizing the tissue and potentially obscuring underlying heterogeneity. Nonetheless,Lucidenic-acid-A a handful of genes have been identified as being expressed in subsets of RPCs including some genes that displayed a temporally restricted expression pattern. However, it was unclear from these studies how similar or different individual RPCs were relative to each other, both across developmental time and at specific timepoints. To begin to assess the degree of gene expression heterogeneity among RPCs, individual retinal cells were harvested from six different developmental timepoints ranging from embryonic day 12.5 through postnatal day 0.