Human embryonic stem cells (hESCs) can be directed toward a variety of different cell fates. The first decision to be made is whether or not to become mesendoderm (ME) or neuroectoderm (NE). In this study, we describe the molecular pathway that leads cells to become NE. Coupled with lineage-specific lengthening of the cell division cycle, we show that the cells change their production of cilia, a sall protrusion from the cell. This in turn stimulated the autophagy pathway, whereby internal cellular components are recycled. Furthermore we found changes in specific transcription factors. Thus, we have identified a primary control axis coupled to cell-cycle progression that directs hESCs toward NE.