Centrosomal protein FOR20 knockout mice display embryonic lethality and left‐right patterning defects

Abstract

Centrosomal protein FOR20 has been reported to be crucial for essential cellular processes, including ciliogenesis, cell migration, and cell cycle in vertebrates. However, the function of FOR20 during mammalian embryonic development remains unknown. To investigate the in vivo function of the For20 gene in mammals, we generated For20 homozygous knockout mice by gene targeting. Our data reveal that homozygous knockout of For20 results in significant embryonic growth arrest and lethality during gestation, while the heterozygotes show no obvious defects. The absence of For20 leads to impaired left-right patterning of embryos and reduced cilia in the embryonic node. Deletion of For20 also disrupts angiogenesis in yolk sacs and embryos. These results highlight a critical role of For20 in early mammalian embryogenesis.

The evolutionary conserved complex CEP90, FOPNL and OFD1 specifies the future location of centriolar distal appendages, and promotes their assembly

“…Consistently, we found that the depletion of either CEP90 or FOPNL decreased the localization at the mother centriole of these distal appendage proteins of about 66% (Figure 6A, B). Altogether, these results suggest that the depletion of either CEP90 or FOPNL prevents the formation of the distal appendages, allowing the understanding of the defective ciliogenesis process previously observed (Wheway et al , 2015; Shen et al , 2020; Sedjaï et al , 2010; Xu et al , 2021). This suggest that FOPNL is a novel and important component for distal appendage assembly.…”

“…Altogether, these results suggest that the depletion of either CEP90 or FOPNL prevents the formation of the distal appendages, allowing the understanding of the defective ciliogenesis process previously observed (Wheway et al, 2015;Shen et al, 2020;Sedjaï et al, 2010;Xu et al, 2021). This suggest that FOPNL is a novel and important component for distal appendage assembly.…”

“…Previous work highlighted a role for FOPNL in ciliogenesis, since its depletion in mammalian cells inhibits cilia formation (Sedjaï et al , 2010) and FOPNL KO mice show embryonic lethality at about E11.5 with an important decrease of cilia in the embryonic node. As a consequence, the embryos show left-right symmetry defects (Xu et al , 2021). However, the dual localization of FOPNL, at both centrioles and centriolar satellites prevented determining which pool of FOPNL is involved in ciliogenesis, since centriolar satellites are also involved in cilia formation (Sedjaï et al , 2010; Stowe et al , 2012).…”

The evolutionary conserved proteins CEP90, FOPNL, and OFD1 recruit centriolar distal appendage proteins to initiate their assembly

“…Consistently, we found that the depletion of FOPNL decreased the localization at the mother centriole of these distal appendage proteins of about 66% (Fig 6A and 6B). Altogether, these results suggest that the depletion of FOPNL prevents the formation of the distal appendages, allowing the understanding of the defective ciliogenesis process previously observed [26,27,30,31]. This suggests that FOPNL is a novel and important component for distal appendage assembly.…”

“…Previous work highlighted a role for FOPNL in ciliogenesis, since its depletion in mammalian cells inhibits cilia formation [ 26 ] and FOPNL knockout (KO) mice show embryonic lethality at about E11.5 with an important decrease of cilia in the embryonic node. As a consequence, the embryos show left-right symmetry defects [ 27 ]. However, the dual localization of FOPNL, at both centrioles and centriolar satellites, prevented determining which pool of FOPNL is involved in ciliogenesis, since centriolar satellites are also involved in cilia formation [ 26 , 28 ].…”