microPublication biology最新文献

Fibroblast Growth Factor Receptors (FGFRs) play a role in diverse developmental pathways that mediate cell proliferation, cell migration, and cell survival. We use C. elegans as a model to better understand FGFR signaling specificity. C. elegans has a single FGFR, EGL-15 . EGL-15 contains an alternatively spliced exon 5 that results in two isoforms, EGL-15(5A) and EGL-15(5B), that differ in their extracellular domains. The EGL-15(5A) isoform is required for the chemoattraction of a pair of migrating sex myoblasts, whose correct positioning is required for egg laying. Deletion of the 5A domain results in an egg-laying defective (Egl) organism. We identified six highly conserved amino acids within the 5A domain and found that two amino acids, S145 and L148 are specifically required for sex myoblast migration in C. elegans .

Signaling by the LET-60 Ras GTPase/ MPK-1 Extracellular Regulated Kinase pathway specifies the vulva cell fate in C. elegans . The let-7 miRNA family negatively regulates LET-60 Ras but other miRNAs can also modulate vulva induction. To determine the impact of globally reducing miRNA function on LET-60 Ras-mediated vulva induction we analyzed the effect of loss of the ALG-1 miRNA regulator on vulva development . Contrary to our expectations, we find that ALG-1 promotes vulva induction independently of LET-60 Ras. We found that the reduced vulva cell fate induction of alg-1 deletion mutants could be due to delayed development of the vulva, or a requirement to maintain the competence of the uninduced precursor cells.

Microsporidia are common natural pathogens of the nematode Caenorhabditis elegans . Infection of C. elegans by the microsporidian species Nematocida parisii leads to induction of the Intracellular Pathogen Response (IPR), including transcriptional upregulation of 26 pals genes. The divergent ' pals ' sequence signature is conserved with humans, but PALS proteins have unknown biochemical functions. So far, none of the 26 induced pals genes have a demonstrated role in immunity. Here, we use RNAseq data, RNA interference, and CRISPR/Cas9 mutant analysis to identify the N. parisii -induced pals-14 gene as an immune gene that provides defense against microsporidia infection in C. elegans .

The mechanisms that anchor microtubules to epithelial junctions are poorly understood. Here we show that recombinant purified paracingulin ( CGNL1 , JACOP), a cytoplasmic junctional protein, decorates microtubules by negative staining electron microscopy and co-pellets with microtubules. Co-pelleting experiments using fragments of CGNL1 indicate that this is mediated by a central region of the CGNL1 head domain (residues 250-420). Deletion of a basic amino-acid stretch (365-377) within this fragment, abolishes both co-pelleting with and decoration of microtubules. These results suggest that paracingulin can interact directly with microtubules through a basic amino-acid stretch of its head domain.

α-synuclein (αSyn) and S129 phosphorylated αSyn (pSyn) define synucleinopathies like Parkinson's disease (PD). Targeting S129 αSyn kinases, like the Polo-like kinase (PLK) family, could provide a therapeutic strategy to limit degeneration of cells bearing aggregated αSyn inclusions. Using longitudinal in vivo multiphoton imaging in mouse cortex after αSyn inclusion induction, we find an increase in cell survival of inclusion-bearing neurons after PLK inhibition. PLK inhibition is associated with increased αSyn levels within inclusions and increased nuclear DNA damage repair markers. Overall, these findings suggest that PLK inhibition may serve as a potential therapeutic strategy for limiting neurodegeneration in PD.

Dominant gain-of-function alleles for the homeotic gene Ultrabithorax ( Ubx ) have been known for a long time. They are summarized under the name Contrabithorax ( Cbx ). Such alleles are rather easy to spot because the morphology of the conspicuous dorsal wing appendage is often dramatically changed. The majority of these alleles is associated with chromosomal rearrangements that alter the genetic landscape of the Ultrabithorax locus. Thereby, UBX protein is ectopically expressed in the wing primordium where it is normally absent. Since Ubx specifies haltere identity, wing cells expressing UBX are determined to become haltere cells. However, apart from the prototypic allele Cbx-1 , information on the molecular details of Contrabithorax alleles is scarce. Here, we present a rather detailed account on a novel Cbx-1-like allele called Cbx-Basel . The results of our study corroborate the model that has been postulated for the Cbx-1 wing phenotype.

Many animals are drawn to prominent sensory cues. Larval zebrafish consistently show attraction to minute water motions (mWMs). This positive mechanotaxis involves scanning-like eye movements (EMs) and changes in body orientation (pivoting), which likely enhance sensory detection. Video analysis shows that EMs increase during mWMs and negatively correlate with locomotion. Both the strength of mWMs and rearing conditions influence EM frequency, with alterations occurring after mWM offset. Additionally, EMs often accompany pivoting. The quantitative data presented here will aid in further exploring the neural bases of visual responses and positive mechanotaxis.

Division of labor, the specialization of subsets of individuals in complementary tasks, increases population efficiency and fitness. We explored swarming motility in Pseudomonas aeruginosa quorum sensing mutants as a model for studying the division of labor. Deletion of the signal synthesis genes lasI or rhlI disrupts swarming, but co-culturing ΔlasI and ΔrhlI restores it in a density-dependent manner. This indicates a successful division of labor where ΔrhlI produces the signal necessary for the ΔlasI mutant, and the ΔlasI reciprocates. We used RNA sequencing to identify additional genes potentially involved in division of labor. Our findings underscore P. aeruginosa swarming as a tractable bacterial model for the division of labor among cells-a hallmark of differentiated multicellularity.

During maternal reprogramming of histone methylation in C. elegans , H3K4me is removed by the histone demethylase, SPR-5 , and H3K9me is subsequently added by the histone methyltransferase, MET-2 . Maternal loss of SPR-5 and MET-2 causes inherited phenotypes, such as sterility, in the progeny. Here, we find that knocking down either the H3K4 methyltransferase SET-2 or the H3K36 methyltransferase MES-4 partially rescues the germline in the progeny of spr-5 ; met-2 mutants, suggesting that the inherited sterility may be caused by inherited H3K4 methylation and altered germline transcription.

Saccharomyces cerevisiae , Baker's yeast, is a well-studied model eukaryotic organism. Much of our knowledge about eukaryotic cell function comes from yeast studies, though nearly 10% of yeast genes remain uncharacterized. This study focuses on YKR004C, a verified gene of unknown function named ECM9 , predicted to be involved in cell division and cell wall maintenance or composition based on previous studies. We investigated the sensitivity in stress conditions of an ECM9 deletion strain, compared to wild-type, to cell wall integrity. These results suggest that ECM9 is involved in cell wall maintenance and the regulatory pathway determining cell division readiness under stress.