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Subcellular localization

Ciliary associated gene, Nucleoplasm, Nucleoli rim

Functional category

• Metabolism
• Signaling (Hedgehog
• GPCRs
• ion channels)
• Ciliary assembly/disassembly

Function

We found that Engrailed 1 (EN1) is highly expressed in serum-free cultured glioma cells as well as glioma tissues, and increased expression level predicts a worse prognosis. EN1 controls glioma cell proliferation, colony formation, migration, and tumorigenic capacity in vivo. It also influences sensitivity of glioma cells to γ-ray irradiation by regulating intracellular ROS levels. Mechanistically, EN1 influences Hedgehog signaling by regulating the level of Gli1 as well as primary cilia length and the primary cilia transport-related protein TULP3(35163043). To understand the implications of an EN1 ko during differentiation, we performed a transcriptome analysis of human neuronal precursor cells (hNPCs) which unveiled alterations in cilia-associated pathways. Further analysis of ciliary morphology revealed an elongation of primary cilia in EN1-deficient hNPCs. Besides, also Wnt signaling pathways were severely affected. Upon stimulating hNPCs with Wnt which drastically increased EN1 expression in WT lines, the phenotypes concerning mitochondrial function and cilia were exacerbated in EN1 ko hNPCs.Conversely, however, ciliogenesis was reduced, but cilia length was increased in both WT and EN1 ko hNPCs following Wnt stimulation (Fig. 9D, E). As many genes involved in the transduction of Wnt signaling were already dysregulated in unstimulated EN1 ko hNPCs (Fig. 9B), it is reasonable to assume that EN1 is also necessary for the fine-tuning of Wnt signaling. In line with this, EN1 ko hNPCs responded more severely than WT cells to Wnt stimulation (Fig. 9D, E). Nevertheless, already in unstimulated EN1 ko hNPCs cilia length was significantly increased, whereas ciliogenesis was not affected (Fig. 9D, E). This indicates an involvement of EN1 in ciliary processes determining cilia length, such as protein sorting or intraflagellar transport(38518837).