Septin-mediated RhoA activation engages the exocyst complex to recruit the cilium transition zone.

Septins are filamentous GTPases that play important but poorly characterized roles in ciliogenesis. Here, we show that SEPTIN9 regulates RhoA signaling at the base of cilia by binding and activating the RhoA guanine nucleotide exchange factor, ARHGEF18. GTP-RhoA is known to activate the membrane targeting exocyst complex, and suppression of SEPTIN9 causes disruption of ciliogenesis and mislocalization of an exocyst subunit, SEC8.

Genetic overview of postaxial polydactyly: Updated classification.

Polydactyly or polydactylism, also known as a hyperdactyly, is a congenital limb defect with various morphologic phenotypes. Apart from physical and functional impairments, the presence of polydactyly is an indication of an underlying syndrome in the newborn. Usually, it follows as an autosomal dominant/recessive inheritance pattern with defects in the limb development's anteroposterior patterning.

Biallelic variant in DACH1, encoding Dachshund Homolog 1, defines a novel candidate locus for recessive postaxial polydactyly type A.

Polydactyly or hexadactyly is characterized by an extra digit/toe with or without a bone. Currently, variants in ten genes have been implicated in the non-syndromic form of polydactyly. DNA from a single affected individual having bilateral postaxial polydactyly was subjected to whole exome sequencing (WES), followed by Sanger sequencing.

Nonredundant roles of DIAPHs in primary ciliogenesis.

Primary cilia are hubs for several signaling pathways, and disruption in cilia function and formation leads to a range of diseases collectively known as ciliopathies. Both ciliogenesis and cilia maintenance depend on vesicle trafficking along a network of microtubules and actin filaments toward the basal body. The DIAPH (Diaphanous-related) family of formins promote both actin polymerization and microtubule (MT) stability.

Revised subunit order of mammalian septin complexes explains their in vitro polymerization properties.

Septins are conserved GTP-binding cytoskeletal proteins that polymerize into filaments by end-to-end joining of hetero-oligomeric complexes. In human cells, both hexamers and octamers exist, and crystallography studies predicted the order of the hexamers to be SEPT7-SEPT6-SEPT2-SEPT2-SEPT6-SEPT7, while octamers are thought to have the same core, but with SEPT9 at the ends. However, based on this septin organization, octamers and hexamers would not be expected to copolymerize due to incompatible ends.