Shh protein can induce Foxa2 and Gefitinib EGFR/HER2 inhibitor ventralize neural progenitors and, in a positive regulatory loop, FOXA2 can induce endogenous SHH and inhibit NKX2.2 and also the serotonergic phenotype. Endogenous transcription of FGF8 resulting from RA exposure can induce WNT1 expression that cooperatively with FGF8 can induce neural progenitors to differentiate into TH-producing cells. A major group of differentially expressed genes includes transcripts that were down-regulated during differentiation. This group includes genes involved in the cell cycle, mitosis and metabolism as well as genes involved in the development of other germ layer clusters. Several major ESC markers, including OCT4, NANOG, PRDM14, and GAL, were grouped in this cluster. Because OTX2, a gene involved in forebrain-hindbrain patterning, was also downregulated during differentiation, the results suggest that posteriorized neurons were generated during differentiation in this study. Matrix associated genes, including MMP1, THBS1, and ITGB1BP3, were also among the hESC enriched genes, suggesting that expression of these genes provides an environment conducive to the proliferation of stem cells. DNA methyltransferase genes and noncoding genes homologous to OCT4 control the epigenetic state of hESCs and are important classes of genes for stem cell maintenance. Some antagonists of FGF signaling, such as SPRY1, were also overrepresented in hESCs. SPRY1 is involved in cortical neuron pattern formation and inhibits caudal cell fates ; its role in hESCs with a high concentration of FGF is not clear and may be important for the fine tuning of FGF signaling in ESCs. Overall, our study found that the transcriptome is extremely complex and dynamic during early neural differentiation of hESCs. All transcripts that were modulated during differentiation were placed in upregulated and downregulated clusters and were analyzed using the KEGG pathway database and ClueGO software. With a two-sided hypergeometric test, genes were assigned to pathways. The pathway information for each cluster was analyzed, and pathways represented in each cluster were identified and compared. Our results showed that some transcripts that were involved in metabolic pathways were downregulated during differentiation. Torin 1 Pentose and glucuronate interconversions, fatty acid turnover , DNA replication, mismatch repair, recombination and immune response pathways were hyper expressed in hESCs, but not in neurons. Nucleotide metabolism and cell cycle pathway members were also highly expressed in hESCs. Genes involved in nitrogen metabolism, apoptosis, NOTCH signaling, axon guidance, neurotrophin signaling, Parkinson��s disease and prion disease are highly abundant molecular pathways that were overrepresented in differentiated neural cells.