Retrograde signaling in biology is the process where a signal travels backwards from a target source to its original source. For example, the nucleus of a cell is the original source for creating signaling proteins. During retrograde signaling, instead of signals leaving the nucleus, they are sent to the nucleus. In cell biology, this type of signaling typically occurs between the mitochondria or chloroplast and the nucleus. Signaling molecules from the mitochondria or chloroplast act on the nucleus to affect nuclear gene expression. In this regard, the chloroplast or mitochondria act as a sensor for internal external stimuli which activate a signaling pathway. In neuroscience, retrograde signaling (or retrograde neurotransmission) refers more specifically to the process by which a retrograde messenger, such as anandamide or nitric oxide, is released by a postsynaptic dendrite or cell body, and travels "backwards" across a chemical synapse to bind to the axon terminal of a presynaptic neuron. In cell biology Retrograde signals are transmitted from plastids to the nucleus in plants and eukaryotic algae, and from mitochondria to the nucleus in most eukaryotes. Retrograde signals are generally considered to convey intracellular signals related to stress and environmental sensing. Many of the molecules associated with retrograde signaling act on modifying the transcription or by directly binding and acting as a transcription factor. The outcomes of these signaling pathways vary by organism and by stimuli or stress. Evolution Retrograde signaling is believed to have arisen after endocytosis of the mitochondria and chloroplast billions of years ago. Originally believed to be photosynthetic bacteria, the mitochondria and chloroplast transferred some of their DNA to the membrane protected nucleus. Thus, some of the proteins required for the mitochondria or chloroplast are within the nucleus. This transfer of DNA further required a network of communication to properly respond to external and internal signals and produce requisite proteins. In yeast The first retrograde signaling pathways discovered in yeast is the RTG pathway. The RTG pathway plays an important role in maintain the metabolic homeostasis of yeast. Under limited resources the mitochondria must maintain a balance of glutamate for the citric acid cycle. Retrograde signaling form the mitochondria initiates production precursor molecules of glutamate to properly balance supplies within the mitochondria. Retrograde signaling can also act to arrest growth if problems are encountered. In Saccharomyces cerevisiae, if the mitochondria fails to develop properly, they will stop growing until the issue is addressed