Laboratory for Axial Pattern Dynamics | RIKEN BDR

Laboratory for Axial Pattern Dynamics

Team Leader

Hidehiko InomataPh.D.

  • Location:Kobe / Developmental Biology Buildings
  • E-mail:hidehiko.inomata[at]riken.jpPlease replace [at] with @.

Understanding and regulating developmental systems from morphogen-mediated patterning

Research Summary

Developmental processes take place through the exchange of information by cells within the constrained spatial environment of the embryo. Such intercellular communication is essential for the formation of a well-ordered body; in its absence, our individual cells would behave in an uncoordinated fashion, and fail to follow the patterns needed for the development of the head, limbs, or other body parts. Factors that play central roles in such developmental signaling are known as morphogens.

In our research we will seek to gain a deeper understanding into processes informed by positional information in a spatial context (developmental fields), using vertebrate (mainly frog and zebrafish) axis formation as a model. The establishment of the frog dorsoventral axis depends on gradients of morphogens secreted by the organizer region. In order to ensure that development based on simple concentration gradients is stably reproducible, cell-cell communications mediated by morphogens need to be robust against perturbations. One example of such robustness can be seen in the response of a frog embryo when bisected; such embryos follow normal developmental patterns, despite being half the ordinary size, a phenomenon known as ‘scaling.’ Our team has previously shown how scaling is maintained through morphogen-mediated intercellular communication when the spatial size of the embryo is perturbed. In our lab, we address visualization of morphogen gradients and in vivo imaging along with biochemical approaches to study how developmental robustness is maintained.

We are also working to develop methods for controlling the shape of morphogen gradients. Gradients are primarily regulated by production, diffusion, and degradation, which indicates that by controlling these factors, it should be possible to arbitrarily design gradients that reconstruct tissue patterns in the embryo. By using such methods, we hope to gain a deeper understanding of developmental systems.

FRAP assays of mEGFP-tagged Sizzled shown by snapshots. From left to right; before bleaching, at the end of bleaching, 50 s after bleaching, and 230 s after bleaching.

Graded DV patterning by the reconstructed organizer. Substantial pSmad accumulation was observed on the side opposite to the reconstructed organizer, indicating that the influence of chordin was distance-sensitive.

Szl-dependent change in the proportion of DV axis. Effects of loss (left) and gain (right) of Sizzled’s function on the DV pattern.

Research Theme

  • Robustness of the developmental system
  • Relationship between extracellular fluid dynamics and distribution of secreted proteins
  • Spatiotemporal regulation of morphogen-mediated patterning

Main Publications List

  • Inomata H, Shibata T, Haraguchi T, and Sasai Y.
    Scaling of dorsal-ventral patterning by embryo size-dependent degradation of Spemann's organizer signals.
    Cell 153. 1296–1311 (2013) doi :10.1016/j.cell.2013.05.004
  • Takai A, Inomata H, Arakawa A, et al.
    Anterior neural development requires Del1, a matrix-associated protein that attenuates canonical Wnt signaling via the Ror2 pathway.
    Development 137. 3293–302 (2010) doi:10.1242/dev.051136
  • Inomata H, Haraguchi T, and Sasai Y.
    Robust stability of the embryonic axial pattern requires a secreted scaffold for chordin degradation.
    Cell 134. 854–865 (2008) doi:10.1016/j.cell.2008.07.008
  • Arakawa A, Matsuo-Takasaki M, Takai A, et al.
    The secreted EGF-Discoidin factor xDel1 is essential for dorsal development of the Xenopus embryo.
    Developmental Biology 306. 160–169 (2007) doi:10.1016/j.cell.2008.07.008
  • Onai T, Matsuo-Takasaki M, Inomata H, et al. XTsh3 is an essential enhancing factor of canonical Wnt signaling in Xenopus axial determination.
    The EMBO Journal 26. 2350–2360 (2007) doi:10.1038/sj.emboj.7601684
  • Inomata H, Nakamura Y, Hayakawa A, et al.
    A scaffold protein JIP-1b enhances amyloid precursor protein phosphorylation by JNK and its association with kinesin light chain 1.
    Journal of Biological Chemistry 278. 22946–22955 (2003) doi: 10.1074/jbc.M212160200