A reduction of primary cilia but not hedgehog signaling disrupts morphogenesis in testicular organoids.

A reduction of primary cilia but not hedgehog signaling disrupts morphogenesis in testicular organoids.
Cell Tissue Res. 2020 Jan 03;:
Authors: Goldsmith TM, Sakib S, Webster D, Carlson DF, Van der Hoorn F, Dobrinski I
Abstract
Most mammalian cells possess a single, non-motile primary cilium that plays an important role in mediating cellular signaling pathways, such as Hedgehog (Hh) signaling. Primary cilia are present on testicular somatic cells and demonstrate a temporal expression during development; however, their role in testicular morphogenesis is not well characterized. To investigate the role of primary cilia and Hh signaling in Sertoli cells on morphogenesis, we inhibited assembly of primary cilia through CRISPR Cas9-mediated gene editing of ODF2, a structural component of primary cilia and siRNA-mediated gene silencing of IFT88, a functional component of the intraflagellar transport system. Knockdown of ODF2 and IFT88 resulted in a 50% reduction in the number of cells with primary cilia and significant shortening of the remaining cilia. The expression of GLI1, a downstream target of Hh signaling, was significantly reduced when IFT88 but not ODF2, was downregulated. When morphogenesis was examined using tubule formation in vitro and a novel testicular organoid system, loss of cilia after knockdown of both targets affected cellular assembly and organization. While the Hh pathway was found to be active during morphogenesis in ...

Source: Cell Research - January 2, 2020 Category: Cytology Authors: Goldsmith TM, Sakib S, Webster D, Carlson DF, Van der Hoorn F, Dobrinski I Tags: Cell Tissue Res Source Type: research