Brocal-Ruiz, Rebeca et al. (2021) International Worm Meeting "Forkhead transcription factor FKH-8 is a master regulator of sensory cilia"

Tena, Juan J., Esteve, Ainara, Mora-Martinez, Carlos, Flames, Nuria, Brocal-Ruiz, Rebeca

[International Worm Meeting, 2021]

Cilia are complex evolutionary conserved eukaryotic structures that, projecting from cell surfaces, perform a variety of biological roles. Cilia are traditionally classified into motile or sensory and hundreds of proteins take part in their composition. This set of genes coding for ciliary components is known as the ciliome. Mutations in the ciliome underlie an ever-growing group of highly pleiotropic multisystemic diseases globally termed as ciliopathies. These diseases are characterized, among other symptoms, by mental retardation, sensory defects and/or metabolic disorders. Despite an estimated 1 in 1,000 people affected by these diseases, the molecular bases of the ciliopathies are still poorly understood. Proper cilium assembly and functionality requires the tightly co-regulated expression of ciliary components; however, little is known about the regulatory logic controlling ciliome transcription. Most ciliome genes are shared between motile and sensory cilia. RFX transcription factors (TFs) have an evolutionarily conserved role in the transcriptional regulation of both motile and sensory ciliome. In vertebrates, transcription of the motile ciliome is also directly regulated by FoxJ1, a Forkhead (FKH) TF. However, to date, TFs working together with RFX in the transcription of the sensory ciliome are unknown in any organism. We have identified FKH-8, a FKH TF, as a terminal selector of the sensory ciliome in C. elegans. fkh-8 expression is restricted to the sixty ciliated sensory neurons of C. elegans, it binds the regulatory regions of the sensory ciliome, it is required for correct ciliome gene expression and cilium morphology and acts synergistically with DAF-19/RFX TF. Accordingly, fkh-8 mutants display a wide range of behavioral defects in a plethora of sensory mediated paradigms, including olfaction, gustation, and mechano-sensation. Importantly, ciliome expression defects in fkh-8 mutants can be rescued by mammalian FoxJ1 but not other FKH TFs. Thus, we have identified, for the first time, a TF that acts together with RFX TFs in the direct regulation of the sensory ciliome. Moreover, together with previous work, our results show that FKH and RFX TFs act together in the regulation of both motile and sensory cilia, suggesting this regulatory logic could be an ancient trait pre-dating functional sub-specialization of cilia. Finally, our results could help better understand the biological basis of orphan ciliopathies.

Ruiz, Manuel (2021) International Worm Meeting "Glucose impacts HSN morphology and induces an egg-laying defective phenotype dependent of the serotonin-signaling pathway"

Ruiz, Manuel

[International Worm Meeting, 2021]

Glucose impacts HSN morphology and induces an egg-laying defective phenotype dependent of the serotonin-signaling pathway Manuel Axel Ruiz and Pamela Padilla Peripheral neuropathy is a common and often painful complication that results from a chronic state of hyperglycemia. In recent years, research has shown that in humans altered levels of serotonin is highly associated to a chronic state of hyperglycemia. Additionally, altered levels of serotonin are associated with various neurological disorders. However, the mechanism by which hyperglycemia impacts serotonin processes is not understood. Here we are using the genetic model system Caenorhabditis elegans as a hyperglycemia model to further understand the impact of a glucose-supplemented diet on the animal's egg-laying behavior. C. elegans possess a nervous system that is composed of 302 neurons. In C. elegans the Hermaphrodite-Specific serotonergic motor Neurons (HSN) play an essential role in regulating egg-laying. Using this model organism, we conducted genetic and cell biological analysis to examine the role a glucose-supplemented diet has on the serotonergic HSN motor neurons. Our preliminary data shows that a glucose-supplemented diet impacts egg-laying and HSN morphology. A significant proportion of animals raised in a glucose-supplemented diet have a higher incidence of intra-uterine egg-hatching, HSN axonal degeneration, and abnormal HSN morphology. We used genetic mutants to dissect out the role the serotonin pathway has on the response to a glucose diet. Furthermore, through RNA-sequencing, we examined how a glucose-supplemented diet alters the expression of genes responsible of serotonergic functions. This work will lead to the further understanding of the molecular mechanisms that are involved on altered serotonergic neuronal functions as a result of a chronic hyperglycemic state.

Juan C Rodriguez-Aguilera et al. (2005) International Worm Meeting "Coq-8 gene links bioenergetics with development and aging in C. elegans."

Angela Gavilan, Juan C Rodriguez-Aguilera, Juan Cabello, Rafael Vazquez-Manrique, Ralf Schnabel, Placido Navas, Howard Baylis, Claudio Asencio

[International Worm Meeting, 2005]

Genes involved in coenzyme Q (Q) biosynthesis, such as coq-7/clk-1, have regulatory functions in Caenorhabditis elegans aging and development. Silencing of C. elegans coq genes lead to life span extension (Asencio et al. 2003). Mutants of coq genes have been reported for coq-7/clk-1 and coq-3. Only coq-7/clk-1 mutant strains have been established, whereas coq-3 knockouts are lethal (Hihi et al. 2002). We show that coq-8 knock-out animals developed until L3 larval stage and then arrested. Mutants did not develop mature gonads, and showed shortened life span under dietary Q-free conditions. We also constructed a COQ-8::GFP reporter under control of coq-8 promoter. An age-dependent pattern of coq-8 gene expression from the embryo to senescence is reported, providing genetic evidence for Q biosynthesis regulation during development and aging. COQ-8 expression started in a few blastomeres as early as of 8th embryo mitosis and increased during larval stages in several tissues, particularly in those with active bioenergetics such as muscle, nervous system and hypodermis throughout moulting period. Maximal COQ-8 expression was detected in L3 stage, matching with the maximal Q content (Jonassen et al. 2002), and the arresting stage in coq-8 knockouts. Non-moulting young adults did not show hypodermis COQ-8 expression and in elderly individuals expression was detected only observed in nervous system. We propose a role for coq-8 gene supporting the regulated Q biosynthesis that fulfils ubiquinone requirements in different tissues during life cycle in C. elegans. References: Asencio, C.; Rodriguez-Aguilera, J. C.; Ruiz-Ferrer, M.; Vela, J., and Navas, P. Silencing of ubiquinone biosynthesis genes extends life span in Caenorhabditis elegans. FASEB J. 2003 Jun; 17(9):1135-7. Hihi, A. K.; Gao, Y., and Hekimi, S. Ubiquinone is necessary for Caenorhabditis elegans development at mitochondrial and non-mitochondrial sites. J Biol Chem. 2002 Jan 18; 277(3):2202-6. Jonassen, T.; Marbois, B. N.; Faull, K. F.; Clarke, C. F., and Larsen, P. L. Development and fertility in Caenorhabditis elegans clk-1 mutants depend upon transport of dietary coenzyme Q8 to mitochondria. J Biol Chem. 2002 Nov 22; 277(47):45020-7.