Vidal Iglesias, Berta et al. (2013) International Worm Meeting "Role of sox-2 in postembryonic lineage progression."

Vidal Iglesias, Berta, Hobert, Oliver

[International Worm Meeting, 2013]

sox-2 is a highly conserved transcription factor that is well known to be a stem cell master regulator and is one of the Yamanaka factors required for the generation of induced pluripotent stem cells. sox-2 has also been extensively associated to neurogenesis and plays an important role in the maintenance of neural stem cells. Using a fosmid-based reporter gene we have seen that sox-2 is expressed broadly during C. elegans embryogenesis, being expressed in several neuronal progenitors, although not exclusively neither in all of them. The sox-2 null mutant is L1 lethal and has the pharynx unattached; however, quantification of a panneuronal reporter does not show any neuronal specification defects, indicating that sox-2 is dispesable for C. elegans embryonic neurogenesis. Interestingly, at the L1 stage, sox-2 is also expressed in several postembryonic blast cells, which have to keep dividing during larval development to give rise to different postembryonic lineages that generate neurons among other cell types. Being sox-2 an important pluripotency factor, we hypothesized that it might be required in the L1 blast cells to retain their developmental potential. Using mosaic analysis strategies to overcome the L1 lethality of the sox-2 null allele, we have so far identified defects in three different postembryonic lineages in the absence of sox-2: the V5 lineage, which originates the postdeirid, the K lineage that gives rise to the DVB neuron and the B lineage, which generates the spicules in males. These results support the idea that postembryonic blast cell competence is compromised in the absence of sox-2. The extent of sox-2 functions in different postembryonic lineages and its mechanism of action to control lineage progression are currently being investigated.

Vidal Iglesias, Berta et al. (2015) International Worm Meeting "How are unilateral neurons specified? The role of Notch."

Hobert, Oliver, Vidal Iglesias, Berta

[International Worm Meeting, 2015]

The nervous system of the nematode C. elegans is mostly bilaterally symmetric. The vast majority of neurons come in left/right pairs, which typically arise from left/right homolog symmetric lineages. However there are exceptions and we can find a few examples of single, unpaired neurons. Thus the overall symmetry of certain lineages has to be broken in order to originate these unilateral neurons. We are investigating the role of cell-cell interactions mediated by the highly conserved Notch signaling pathway in the generation of unilateral neurons. There are several well-established Notch inductive signaling events important to specify cell fates during C. elegans embryogenesis. We show that in Notch mutants some unilateral neurons are not generated while others are now duplicated and symmetrized. Some of these effects can be attributed to the previously described 4th Notch interaction between the blastomeres MSapa/p and ABplpapp, which is required for the specification of the excretory cell. However the observed effects in other unilateral neurons must be the result of previously unknown Notch interactions, which we are in the process of characterizing further. .

Vidal Iglesias, Berta et al. (2011) International Worm Meeting "Sox genes in early nervous system development."

Vidal Iglesias, Berta, Hobert, Oliver

[International Worm Meeting, 2011]

One of the first steps in nervous system development is the generation of neural progenitor cells that will subsequently give rise to the vast diversity of neurons present in the adult. How neuronal progenitor specification is achieved is a fundamental question that we are still far away from completely understanding. The Sox proteins are a highly conserved group of transcription factors and the expression of some of them (group B) correlates with the commitment of cells to a neural fate. The evolutionary conserved expression of sox genes in neuronal progenitors and the fact that they are regulated by signaling molecules involved in neuronal specification suggests a role for sox genes in establishing neural fate. However, the relevance of Sox proteins in vertebrate neuronal development has been difficult to prove genetically mainly because of presumed redundant functions. C. elegans has only 5 sox genes (sem-2, sox-2, sox-3, sox-4 and egl-13) and we have investigated their potential role in early neurogenesis. First, we have analyzed the expression pattern of all sox genes during embryogenesis by using fosmid-based reporter genes. sem-2 and sox-2 are the sox genes expressed earliest and in a more broad manner during embryogenesis, being expressed in neuron progenitors, although not exclusively neither in all of them. Their expression pattern would be be compatible with a role in early neuronal specification. On the other hand, sox-3, sox-4 and egl-13 are expressed in a few cells during late embryogenesis, when most neurons are already born. Hence, we have mainly focused our efforts in further characterizing sem-2 and sox-2 as potential regulators of early neuronal specification events. For that purpose we have generated a new sox-2 deletion allele taking advantage of the MosDel tecnique. Both sem-2 and sox-2 null mutants are embryonic or early larval lethal and show different degrees of morphogenesis defects. When we crossed sem-2 or sox-2 mutants with a panneuronal reporter we did not observe any obvious neuronal loss and the expression of neuron-type specific reporters was not generaly affected either. These results strongly suggest that, contrary to our initial hypothesis, sox genes are not required for correct neuronal specification. The possibility of sem-2 and sox-2 acting redundantly is unlikely, at least in a broad manner, since their co-expression during embryogenesis in rather limited. Potential redundancy or compensatory mechanisms between different sox genes are currently being investigated.

Vidal Iglesias, Berta et al. (2021) International Worm Meeting "A homeodomain transcription factor required to specify all pharyngeal neurons"

Vidal Iglesias, Berta, Hobert, Oliver, Gulez, Burcu

[International Worm Meeting, 2021]

In addition to their central nervous system ("brain"), all complex multicellular organisms contain an enteric nervous system that controls the activity of fore-, mid- and/or hindgut. The foregut in C. elegans is the pharynx, which contains its own nervous system, the pharyngeal nervous system, composed of only 20 neurons belonging to 14 different types. These neurons form a self-contained circuit that controls pharyngeal pumping. Most pharyngeal neurons directly connect to end organs and can be considered polymodal, with sensory-inter-motor characteristics, a feature that is reminiscent of primitive nervous systems. Thus, understanding how pharyngeal neurons are specified during development might shed light on fundamental aspects of neuronal development and evolution. ceh-34, a homeodomain transcription factor of the Six family, is continuously expressed in all pharyngeal neurons and no other neurons outside of the pharynx. Remarkably, we have found that in ceh-34 mutants, pharyngeal neurons are generated, but they all fail to express a wide array of neuron-type identity genes, including neurotransmitter pathway genes, indicating that the communication within the circuit is completely disrupted. Also, the anatomy of the pharyngeal neurons (i.e. axon pathfinding) seems to be highly disorganized. These results show that ceh-34 acts as a pharyngeal neuron master regulator ("terminal selector") that defines the identity of individual neurons and assembles them into functional circuitry. Moreover, a conditional AID-based allele demonstrates that ceh-34 is continuously required during the life of the worm to maintain pharyngeal neuron identity. We hypothesize that ceh-34 acts together with other transcription factors to form a combinatorial code that gives each pharyngeal neuron its unique identity and we have started to identify such factors (see abstract by B. Gulez et al). We find that ceh-34 expression is regulated by the pharynx organ selector pha-4 indicating that this organ selector utilizes distinct downstream selector genes to pattern distinct tissue types within the pharynx.

Alqadah, Amel et al. (2013) International Worm Meeting "Postmitotic diversification of olfactory neuron types is mediated by differential activities of the HMG-box transcription factor SOX-2."

Alqadah, Amel, Hsieh, Yi-Wen, Hobert, Oliver, Chang, Chieh, Chuang, Chiou-Fen, Vidal Iglesias, Berta

[International Worm Meeting, 2013]

The nervous system is composed of an immense variety of different cell types. This is especially important in the developing sensory system, which generates a large number of specialized neurons for sensing various stimuli in the environment. However, the molecular mechanisms that regulate sensory neuron diversity are only partly understood. In the C. elegans olfactory system, AWA, AWB, and AWC neurons are dedicated to sensing volatile odorants. Here we reveal a novel role of the highly conserved HMG-box transcription factor SOX-2 in post-mitotic specification as well as alternative differentiation of AWC and AWB olfactory neurons. From a non-biased forward genetic screen, we identified a missense mutation in the HMG domain of the SOX-2 protein that results in a cell fate transformation from AWB to AWC at both molecular and functional levels. This phenotype is similar to that caused by loss-of-function mutations in the homedomain protein LIM-4. Analysis of a sox-2 null allele reveals functions of sox-2 in postmitotic cells to specify general identities of both AWC and AWB neurons. We show that SOX-2 functions cooperatively with the OTX/OTD transcription factor CEH-36 to specify the AWC cell fate, and that SOX-2 and LIM-4 function cooperatively to further differentiate AWB from AWC fates. Together, our results suggest a model in which SOX-2 partners with different transcription factors such as LIM-4 or CEH-36 to diversify postmitotic olfactory cell types. Sox2 plays an important role in the maintenance of neural progenitor/stem cell pluripotency and inhibition of neurogenesis in the developing nervous system. Our study demonstrates that sox-2 is reused in postmitotic cells to regulate alternative differentiation of two olfactory neurons.

Landler L et al. (2018) Elife "Comment on "Magnetosensitive neurons mediate geomagnetic orientation in Caenorhabditis elegans"."

Nordmann GC, Papadaki-Anastasopoulou A, Keays DA, Landler L, Hochstoeger T, Nimpf S

[Elife, 2018]

A diverse array of species on the planet employ the Earth's magnetic field as a navigational aid. As the majority of these animals are migratory, their utility to interrogate the molecular and cellular basis of the magnetic sense is limited. Vidal-Gadea and colleagues recently argued that the worm <i>Caenorhabditis elegans</i> possesses a magnetic sense that guides their vertical movement in soil. In making this claim, they relied on three different behavioral assays that involved magnetic stimuli. Here, we set out to replicate their results employing blinded protocols and double wrapped coils that control for heat generation. We find no evidence supporting the existence of a magnetic sense in <i>C. elegans</i>. We further show that the Vidal-Gadea hypothesis is problematic as the adoption of a correction angle and a fixed trajectory relative to the Earth's magnetic inclination does not necessarily result in vertical movement.

Walhout AJM et al. (2000) Science "Protein interaction mapping in C. elegans using proteins involved in vulval development."

Sordella R, Hartley JL, Lu WX, Thierry-Mieg N, Walhout AJM, Brasch MA, Temple GF, Vidal MI

[Science, 2000]

Protein interaction mapping using large-scale two-hybrid analysis has been proposed as a way to functionally annotate large numbers of uncharacterized proteins predicted by complete genome sequences. This approach was examined in Caenorhabditis elegans, starting with 27 proteins involved in vulval development. The resulting map reveals both known and new potential interactions and provides a functional annotation for approximately 100 uncharacterized gene products. A protein interaction mapping project is now feasible for C. elegans on a genome-wide scale and should contribute to the understanding of molecular mechanisms in this organism and in human diseases.AD - Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.FAU - Walhout, A JAU - Walhout AJFAU - Sordella, RAU - Sordella RFAU - Lu, XAU - Lu XFAU - Hartley, J LAU - Hartley JLFAU - Temple, G FAU - Temple GFFAU - Brasch, M AAU - Brasch MAFAU - Thierry-Mieg, NAU - Thierry-Mieg NFAU - Vidal, MAU - Vidal MLA - engID - 1 R21 CA81658 A 01/CA/NCIID - 1 RO1 HG01715-01/HG/NHGRIPT - Journal ArticleCY - UNITED STATESTA - ScienceJID - 0404511RN - 0 (Genetic Vectors)RN - 0 (Helminth Proteins)RN - 0 (LIN-35 protein)RN - 0 (LIN-53 protein)RN - 0 (Repressor Proteins)RN - 0 (Retinoblastoma Protein)SB - IM

Labrousse AM et al. (1999) Worm Breeder's Gazette "The on-ramp, off-ramp, Nramp family."

Labrousse AM, Ewbank JJ

[Worm Breeder's Gazette, 1999]

We are interested in investigating the function of nematode homologues of proteins known to be important for innate immunity in other organisms. Genetic studies with the mouse have shown that a single locus is involved in innate resistance against a range of pathogens including Mycobacterium bovis (BCG), M. intracellulare, M. lepraemurium, Salmonella typhirium and Leishmania. The corresponding gene codes for a protein Nramp1 (Natural resistance-associated macrophage protein; Vidal et al., 1993, Cell, 73, 469-485) that is specifically expressed in macrophages. A highly similar protein, Nramp2, is expressed ubiquitously and appears not to have a role in defense against infection. The Nramp proteins are members of a family of metal ion transporters, that includes the yeast Smf proteins.

Filingeri D (2015) J Neurophysiol "Humidity sensation, cockroaches, worms, and humans: are common sensory mechanisms for hygrosensation shared across species?"

Filingeri D

[J Neurophysiol, 2015]

Although the ability to detect humidity (i.e., hygrosensation) represents an important sensory attribute in many animal species (including humans), the neurophysiological and molecular bases of such sensory ability remain largely unknown in many animals. Recently, Russell and colleagues (Russell J, Vidal-Gadea AG, Makay A, Lanam C, Pierce-Shimomura JT. Proc Natl Acad Sci USA 111: 8269-8274, 2014) provided for the first time neuromolecular evidence for the sensory integration of thermal and mechanical sensory cues which underpin the hygrosensation strategy of an animal (i.e., the free-living roundworm Caenorhabditis elegans) that lacks specific sensory organs for humidity detection (i.e., hygroreceptors). Due to the remarkable similarities in the hygrosensation transduction mechanisms used by hygroreceptor-provided (e.g., insects) and hygroreceptor-lacking species (e.g., roundworms and humans), the findings of Russell et al. highlight potentially universal mechanisms for humidity detection that could be shared across a wide range of species, including humans.

Moon, K. et al. (2019) International Worm Meeting "Gait selection of Caenorhabditis elegans is regulated by mechanosensitive DEG/ENaC channels."

Moon, K., Kim, K., Kim, J., Yeon, J.

[International Worm Meeting, 2019]

Animals change their locomotion or gaits in response to environmental condition. In vertebrates, gait transition has been shown to be mediated by monoamines, which is conserved across many species including the nematode Caenorhabditis elegans (Vidal-Gadea et al., 2011). However, molecular mechanisms of gait transition are still unclear. C. elegans exhibits two gaits, swimming in liquids and crawling on dense gels. C. elegans genome contains evolutionarily conserved 28 DEG/ENaC channels, of which functions may be involved in mechanosensory transduction and locomotion (Goodman and Schwarz, 2003). We first hypothesized that mechanosensitive channels could act as a gait transition initiator and examined crawl-to-swim transition phenotype in DEG/ENaC mutants. We found that while acd-5 mutants show normal crawling, transition from crawling to swimming upon liquid exposure is defective, suggesting roles of ACD-5 in gait transition. We are currently generating acd-5 rescue lines and examining expression pattern of acd-5.