Mustn1 is essential for craniofacial chondrogenesis during Xenopus development

Mustn1 is a vertebrate-specific protein that, in vitro, was showed to be essential for prechondrocyte function and thus it has the potential to regulate chondrogenesis during embryonic development. We use Xenopus laevis as a model to examine Mustn1 involvement in chondrogenesis. Previous work suggests that Mustn1 is necessary but not sufficient for chondrogenic proliferation and differentiation, as well as myogenic differentiation in vitro. Mustn1 was quantified and localized in developing Xenopus embryos using RT-PCR and whole mount in situ hybridization. Xenopus embryos were injected with either control morpholinos (Co-MO) or one designed against Mustn1 (Mustn1-MO) at the four cell stage. Embryos were scored for morphological defects and Sox9 was visualized via in situ hybridization. Finally, Mustn1-MO-injected embryos were co-injected with Mustn1-MO resistant mRNA to confirm the specificity of the observed phenotype. Mustn1 is expressed from the mid-neurula stage to the swimming tadpole stages, predominantly in anterior structures including the pharyngeal arches and associated craniofacial tissues, and the developing somites. Targeted knockdown of Mustn1 in craniofacial and dorsal axial tissues resulted in phenotypes characterized by small or absent eye(s), a shortened body axis, and tail kinks. Further, Mustn1 knockdown reduced cranial Sox9 mRNA expression and resulted in the loss of differentiated cartilaginous head structures (e.g. ceratohyal and pharyngeal arches). Reintroduction of MO-resistant Mustn1 mRNA rescued these effects. We conclude that Mustn1 is necessary for normal craniofacial cartilage development in vivo, although the exact molecular mechanism remains unknown.     

Photosynthesis is limited at high leaf to air vapor pressure deficit in a mutant of Arabidopsis thaliana that lacks trienoic fatty acids

We have investigated the role of polyunsaturated fatty acids in photosynthesis using a triple mutant of Arabidopsis thaliana that lacks trienoic fatty acids (fad 3-2 fad 7-2 fad 8). Though this mutant is male sterile, vegetative growth and development under normal conditions are largely unaffected (McConn and Browse, 1996 Plant Cell 8: 403–416). At 0.2–1.0 kPa vapor pressure deficit (low VPD), maximum photosynthetic rates of wild-type and mutant plants were similar while stomatal conductance rates were up to 2 times higher in mutant plants. However, light-saturated rates of carbon assimilation and stomatal conductance in the mutant were lower than in wild-type plants when measured at ambient (35 Pa) CO₂ and 2.0–2.8 kPa vapor pressure deficit (high VPD). The limitation to photosynthesis in the mutant plants at high VPD was overcome by saturating partial pressures of CO₂ suggesting a stomatal limitation. Chlorophyll fluorescence measurements indicate that differences observed in maximum assimilation rates were not due to limitations within the photochemical reactions of photosynthesis. Stomatal response to VPD and intrinsic water use efficiency was drastically different in mutant versus wild-type plants. The results of this investigation indicate that for Arabidopsis, polyunsaturated fatty acids may be an important determinant of responses of photosynthesis and stomatal conductance to environmental stresses such as high VPD. This revised version was published online in June 2006 with corrections to the Cover Date.     

Correlated evolution between hearing sensitivity and social calls in bats

Echolocating bats are auditory specialists, with exquisite hearing that spans several octaves. In the ultrasonic range, bat audiograms typically show highest sensitivity in the spectral region of their species-specific echolocation calls. Well-developed hearing in the audible range has been commonly attributed to a need to detect sounds produced by prey. However, bat pups often emit isolation calls with low-frequency components that facilitate mother-young reunions. In this study, we examine whether low-frequency hearing in bats exhibits correlated evolution with (i) body size; (ii) high-frequency hearing sensitivity or (iii) pup isolation call frequency. Using published audiograms, we found that low-frequency hearing sensitivity is not dependent on body size but is related to high-frequency hearing. After controlling for high-frequency hearing, we found that low-frequency hearing exhibits correlated evolution with isolation call frequency. We infer that detection and discrimination of isolation calls have favoured enhanced low-frequency hearing because accurate parental investment is critical: bats have low reproductive rates, non-volant altricial young and must often identify their pups within large crèches.     

ER-lysosome lipid transfer protein VPS13C/PARK23 prevents aberrant mtDNA-dependent STING signaling

Mutations in VPS13C cause early-onset, autosomal recessive Parkinson’s disease (PD). We have established that VPS13C encodes a lipid transfer protein localized to contact sites between the ER and late endosomes/lysosomes. In the current study, we demonstrate that depleting VPS13C in HeLa cells causes an accumulation of lysosomes with an altered lipid profile, including an accumulation of di-22:6-BMP, a biomarker of the PD-associated leucine-rich repeat kinase 2 (LRRK2) G2019S mutation. In addition, the DNA-sensing cGAS-STING pathway, which was recently implicated in PD pathogenesis, is activated in these cells. This activation results from a combination of elevated mitochondrial DNA in the cytosol and a defect in the degradation of activated STING, a lysosome-dependent process. These results suggest a link between ER-lysosome lipid transfer and innate immune activation in a model human cell line and place VPS13C in pathways relevant to PD pathogenesis.     

Life-stage specific environments in a cichlid fish: implications for inducible maternal effects

Through environmentally induced maternal effects females may fine-tune their offspring’s phenotype to the conditions offspring will encounter after birth. If juvenile and adult ecologies differ, the conditions mothers experienced as juveniles may better predict their offspring’s environment than the adult females’ conditions. Maternal effects induced by the environment experienced by females during their early ontogeny should evolve when three ecological conditions are met: (1) Adult ecology does not predict the postnatal environmental conditions of offspring; (2) Environmental conditions for juveniles are correlated across successive generations; and (3) Juveniles occasionally settle in conditions that differ from the juvenile habitat of their mothers. By combining size-structured population counts, ecological surveys and a genetic analysis of population structure we provide evidence that all three conditions hold for Simochromis pleurospilus, a cichlid fish in which mothers adjust offspring quality to their own juvenile ecology. In particular we show (1) that the spatial niches and the habitat quality differ between juveniles and adults, and we provide genetic evidence (2) that usually fish of successive generations grow up in similar habitats, and (3) that occasional dispersal in populations with a different habitat quality is likely to occur. As adults of many species cannot predict their offspring’s environment from ambient cues, life-stage specific maternal effects are likely to be common in animals. It will therefore be necessary to incorporate parental ontogeny in the study of parental effects when juveniles and adults inhabit different environments.     

Regulation of calcium channels by RGK proteins

The RGK family of proteins, small GTPases of the Ras superfamily, are known to regulate calcium currents. It is commonly thought that this is due to an interaction with the Cavβ subunit, however, the mechanism of this inhibition is unclear. There have been conflicting reports of whether RGK proteins can affect channel trafficking or whether they reduce calcium currents by interacting with channels at the membrane. In the last year, several studies have emerged which explore the intricacies of RGK protein interaction with the channel itself and the importance of the Cavβ subunit for this interaction, in addition to providing some tantalizing suggestions for the mechanism by which RGK proteins reduce or eliminate calcium currents. In this review, we present an overview of these recent advances and suggest a model that may synthesize these latest works.