Browsing by Subject "EXPRESSION PATTERNS"

Sort by: Order: Results:

Now showing items 1-4 of 4
  • Gonda, Yuko; Namba, Takashi; Hanashima, Carina (2020)
    The formation of the neocortex relies on intracellular and extracellular signaling molecules that are involved in the sequential steps of corticogenesis, ranging from the proliferation and differentiation of neural progenitor cells to the migration and dendrite formation of neocortical neurons. Abnormalities in these steps lead to disruption of the cortical structure and circuit, and underly various neurodevelopmental diseases, including dyslexia and autism spectrum disorder (ASD). In this review, we focus on the axon guidance signaling Slit-Robo, and address the multifaceted roles of Slit-Robo signaling in neocortical development. Recent studies have clarified the roles of Slit-Robo signaling not only in axon guidance but also in progenitor cell proliferation and migration, and the maturation of neocortical neurons. We further discuss the etiology of neurodevelopmental diseases, which are caused by defects in Slit-Robo signaling during neocortical formation.
  • Consortium Refractive Error Myopia; UK Biobank Eye Vision Consortium; Fan, Qiao; Pozarickij, Alfred; Tan, Nicholas Y. Q.; Wedenoja, Juho; Pärssinen, Olavi; Hammond, Christopher J. (2020)
    Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia. Qiao Fan et al. report a genome-wide association analysis of corneal curvature-an important measurement for identifying vision problems, such as myopia-in more than 45,000 individuals of either European or Asian ancestry. They identify 47 loci, 26 of which are novel, with some showing population-specific effects and pleiotropic effects on eye elongation and myopia.
  • Mackenzie, Kathryn Kuligowska; Coelho, Livia Lopes; Lutken, Henrik; Mueller, Renate (2019)
    The PEBP family comprises proteins that function as key regulators of flowering time throughout the plant kingdom and they also regulate growth and plant architecture. Within the PEBP protein family, three subfamilies can be distinguished in angiosperms: MOTHER OF FT AND TFL1-like (MFT), FLOWERING LOCUS T-like (FT-like), and TERMINAL FLOWER1-like (TFL1-like). Taking advantage of the genome sequences available from K. fedtschenkoi and K. laxiflora, we performed computational analysis to identify the members of the PEBP gene family in these species. The analyses revealed the existence of 11 PEBP genes in K. fedtschenkoi and 18 in K. laxiflora, which are clustered in two clades: FT-like and TFL1-like. The PEBP genes had conserved gene structure and the proteins had highly conserved amino acid sequences in the positions crucial for the protein functions. The analysis of Ka/Ks ratio revealed that most recently duplicated genes are under positive selection. Despite being an economically important genus, the genetics underlying the regulation of flowering in Kalanchoe is poorly understood. The results of this study may provide a new insight into the molecular control of flowering that will allow further studies on flowering control in Kalanchoe.
  • Veistinen, Lotta K.; Mustonen, Tuija; Hasan, Md. Rakibul; Takatalo, Maarit; Kobayashi, Yukiho; Kesper, Dorthe A.; Vortkamp, Andrea; Rice, David P. (2017)
    Loss-of-function mutations in GLI3 and IHH cause craniosynostois and reduced osteogeneiss, respectively. In this study, we show that ihh ligand, the receptor Ptch1 and Gli transcription factors are differentialyy expressed in embryonic mouse calvaria osteogenic condenstions. We show that in both ihh(-/-) and Gli3(Xt-J/Xt-J) embroyonic mice, the normal gene expression architecture is lost and this results in disorganized calvarial bone developement. RUNX2 is a master regulatory transciption factor controlling osteogenesis. In the absence of Gli3, RUNX2 isoform II and IHH are upregulated, and RUNX2 isoform I downregulated. This is consistent with the expandeed and aberant osteogenesis observed in Gli3Xt-J/Xt-J mice, and consistent RunX2-t expression by relatively immature osteoprogenitors. ihh-/- mice exhibited small calvarial bones HH target genes, Ptch1 and Gli1, were absent. This indicates that IHH is the functional HH ligand, and that it is not compensated by another HH ligand. To decipher the roles and potential interaction of Gli3 and ihh. we generated ihh-/-; gli3Xt-J/Xt-J compound mutant mice. Even in the absence of ihh, Gli3 deletion was sufficient to induce aberrant precocious ossification across the developing suture, indicating that the carniosyostosis pehnotype of Gli3Xt-J/Xt-J mice is not dependent on IHH ligand. Also we found that ihh was not required for Runx2 expression as the expression of RUNX2 target genes was unaffected by deletion of Ihh. To test whether RUNX2 has a role upstream of IHH we performed RUNX2 siRNA knock down experiements in WT calvarial osteoblasts and explants and found that Ihh expression is suppressed. Our results show that IHH is the functional HH ligand in the embroynic mouse calvaria osteogenic condensations, where it regulates the progression of osteoblastic differentation. As GLI3 represses the expression of Runx2-II abd Ihh, and also elevats the Runx2-I expression, and as IHH may be regulated by RUNX2 these results raise the possibility of a regualtory feedback circuit to control calvarial osteogenesis and suture patency. Taken together RUNX2-controlled osteoblastic cell fate is regulated by IHH through concomitant inhibition of GLI3-repressor formation and activation of downstreams targets.