Another enriched pathway identified by GO analysis of total,up and down regulated DEGs implicated differential regulation in cilium assembly in BPD neurons. Cilium, a microtubule enriched cellular structure, appears to play a key role in developmental signaling cascades, especially associated with hedgehog (Hh) signaling molecules [55]. A report by Breunig et. al. [56] showed that primary cilia are required for Sonic Hedgehog (Shh) pathways and that mutations in ciliary components can lead to phenotypes similar to the phenotypes of Hh/Shh pathway dysregulation, leading to many different pathologies including cognitive deficits and behavioral disorders [55]. A recent report demonstrated that disruption in Shh signaling underlies Ellis-van Creveld dwarfism syndrome, which has a protective effect against development of BPD [57]. This observation, together with our identification of cilium assembly as a pathway modulated in BPD, suggests that disruption in cilial assembly and associated developmental signaling cascade may contribute to BPD pathogenesis.
