The ectoderm is the first germ layer to emerge during gastrulation, which is initiated by the formation of the primitive streak within the epiblast. Cell lineages derived from the ectoderm differentiate to form mainly the epidermis (including skin, hair, nails, and sweat and sebaceous cutaneous glands) and the nervous system (central and peripheral). The development of the vertebrate nervous system is shown to be regulated temporally and spatially by gradients of signaling molecules that may have either inhibitory or activating roles. These molecules are important for neuronal migration (Khodosevich and Monyer, 2011), axonal guidance and outgrowth (Chilton, 2006), interneuronal synapses (Scheiffele, 2003) and neuron-glia interaction (Fields and Stevens-Graham, 2002). Subsequently, experiments have demonstrated that this process is under the control of a combination of small-molecule endogenous inhibitors of bone morphogenic protein (BMP) and TGFβ/activin/nodal signaling (Morizane et al., 2011), which promote highly efficient neural induction from both human ESCs and iPSCs. Additionally, it was shown that DLK1 has a role in stimulating neurogenesis of human and mouse iPSC-derived neural progenitors via modulating Notch and BMP signaling (Surmacz et al., 2012).
