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TAKUYA AKIYAMA
Research Scientist
RESEARCH SUMMARY
Developmental pattern formation
A relatively small number of intercellular signaling molecules, such as the evolutionarily conserved Bone Morphogenetic Protein(BMP), are used repeatedly to create complex body architectures and to maintain homeostasis. BMP acts as a morphogen in a variety of tissues and regulates many developmental events, such as early embryonic axis specification, limb patterning, and stem cell maintenance. The concept of the morphogen gradient is one of the essential cornerstones of modern developmental biology. A morphogen provides positional information to cells in a developmental field and specifies different cell fates in a concentration dependent manner. As a central model for morphogen actions, the BMP2/4-like ligand Decapentaplegic (DPP) directs distinct cell fates in the developing Drosophila wing disc by forming a long-range signaling gradient from a row of its expressing cells. However, the molecular mechanisms by which the endogenous BMP ligand generates the stable activity gradient remain largely unspecified. The goal of my work is to understand how the BMP ligands move across a field of cells and establish an activity gradient.

Impacts of disease-associated somatic mutations on animal development and homeostasis
Alteration of genetic information is a cause of a variety of diseases. Although pathogenesis associated with inherited mutations has been extensively studied, how somatic mutations during development and homeostasis lead to disease conditions remains elusive due to a lack of methods for inducing mutations at the endogenous level. To address this question, I establish an inducible allele switch system at the endogenous locus that allows replacement of wild-type coding sequence with its mutants. Using Drosophila as disease models, I investigate the effects of disease-associated somatic mutations at cellular and tissue levels and aim at deciphering molecular mechanisms underlying disease initiation.

EDUCATION
PhD Biology, Tokyo Metropolitan University, Tokyo, Japan - 2003
MSc Biology, Tokyo Metropolitan University, Tokyo, Japan – 2000
BS Agriculture, University, Aomori, Japan - 1998  

SELECTED PUBLICATIONS
Somatic clones heterozygous for recessive disease alleles of BMPR1A exhibit unexpected phenotypes in Drosophila.
Akiyama, T., User, SD and Gibson, MC.
Elife. 2018 May 10;7. pii: e35258. doi: 10.7554/eLife.35258.
PubMed

Regulation of neuroblast proliferation by surface glia in the Drosophila larval brain.
Kanai, MI., Kim, MJ., Akiyama, T., Takemura, M., Wharton, K., O’Connor, MB., and Nakato, H.
Sci. Rep.
8(1):3730.
PubMed

Drosophila models of FOP provide mechanistic insight.
Le, V., Akiyama, T., and Wharton, KA.
Bone 109:192-200.
PubMed

Decapentaplegic and growth control in the developing Drosophila wing disc.
Akiyama, T., and Gibson, MC.
Nature 527:375-378.
PubMed

Morphogen transport: theoretical and experimental controversies.
Akiyama, T., and Gibson, MC.
Wiley Interdiscip. Rev. Dev. Biol. 4:99-112.
PubMed

A large bioactive BMP ligand with distinct signaling properties is produced by alternative proconvertase processing.
Akiyama, T.
, Marqués, G., and Wharton, KA.
Sci. Signal. 5: ra28.
PubMed

Dally regulates Dpp morphogen gradient formation by stabilizing Dpp on the cell surface.
Akiyama, T., Kamimura, K., Firkus, C., Takeo, S., Shimmi, O. and Nakato, H.
Dev. Biol. 313:408-419.
PubMed