The signals triggering entry into meiosis in metazoans are a very active area of research, and much is still unknown. However, the same basic principles govern the decision to enter the meiotic program in all organisms in which this transition has been studied. Extracellular signals induce a transcriptional program that produces meiosis-specific cell cycle factors that bring about the unusual meiotic cell divisions. This modification of the cell cycle goes hand in hand with a developmental program that induces the features characteristic of gametes, such as the development of a flagellum in sperm or the production of a stress-resistant cell wall during spore formation in fungi. At least one of the extracellular signals inducing entry into meiosis in mammals is retinoic acid, a signaling molecule that, by binding to the transcription factor retinoic acid receptor (RAR), functions in many different developmental processes (see Figure 9-43). The cellular targets of this hormone, and how it functions to specify the meiotic fate, remain to be discovered.

The molecular mechanisms underlying the decision to enter meiosis are well understood in S. cerevisiae. The decision to enter the meiotic divisions is made in G₁. Depletion of nitrogen and carbon sources induces diploid cells to undergo meiosis instead of mitosis, yielding haploid spores (see Figure 1-23). During the meiotic divisions, budding is repressed. Pre-meiotic S phase and the two meiotic divisions thus occur within the confines of the parent cell. Spore walls are then produced around the four meiotic products. Recall that budding and the initiation of DNA replication are induced by G₁/S phase CDKs. Their expression needs to be inhibited to prevent budding. Nutritional starvation represses expression of G₁/S phase cyclins, thereby inhibiting budding. However, DNA replication also relies on G₁/S phase CDKs. How can pre-meiotic DNA replication occur in the absence of G₁/S phase CDKs? The sporulation-specific protein kinase Ime2 takes over the role of G₁/S phase CDKs in promoting DNA replication. Ime2 promotes (1) phosphorylation of the APC/C specificity factor Cdh1, inactivating it so that S phase and M phase cyclins can accumulate (see Figure 19-13); (2) phosphorylation of transcription factors to induce expression of genes whose products are required for S phase, including DNA polymerases and S phase cyclins (see Figure 19-14); and (3) phosphorylation of the S phase CDK inhibitor Sic1, leading to release of active S phase CDKs and the onset of pre-meiotic DNA replication.