@article{18807,
  abstract     = {Developing tissues interpret dynamic changes in morphogen activity to generate cell type diversity. To quantitatively study bone morphogenetic protein (BMP) signaling dynamics in the mouse neural tube, we developed an embryonic stem cell differentiation system tailored for growing tissues. Differentiating cells form striking self-organized patterns of dorsal neural tube cell types driven by sequential phases of BMP signaling that are observed both in vitro and in vivo. Data-driven biophysical modeling showed that these dynamics result from coupling fast negative feedback with slow positive regulation of signaling by the specification of an endogenous BMP source. Thus, in contrast to relays that propagate morphogen signaling in space, we identify a BMP signaling relay that operates in time. This mechanism allows for a rapid initial concentration-sensitive response that is robustly terminated, thereby regulating balanced sequential cell type generation. Our study provides an experimental and theoretical framework to understand how signaling dynamics are exploited in developing tissues.},
  author       = {Rus, Stefanie and Brückner, David and Minchington, Thomas and Greunz, Martina and Merrin, Jack and Hannezo, Edouard B and Kicheva, Anna},
  issn         = {1534-5807},
  journal      = {Developmental Cell},
  number       = {4},
  pages        = {567--580},
  publisher    = {Elsevier},
  title        = {{Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling}},
  doi          = {10.1016/j.devcel.2024.10.024},
  volume       = {60},
  year         = {2025},
}

@article{18601,
  abstract     = {Geometrically controlled stem cell differentiation promotes reproducible pattern formation. Here, we present a protocol to fabricate elastomeric stencils for patterned stem cell differentiation. We describe procedures for using photolithography to produce molds, followed by molding polydimethylsiloxane (PDMS) to obtain stencils with through holes. We then provide instructions for culturing cells on stencils and, finally, removing stencils to allow colony growth and cell migration. This approach yields reproducible two-dimensional organoids tailored for quantitative studies of growth and pattern formation.
For complete details on the use and execution of this protocol, please refer to Lehr et al.1},
  author       = {Rus, Stefanie and Merrin, Jack and Kulig, Monika Aleksandra and Minchington, Thomas and Kicheva, Anna},
  issn         = {2666-1667},
  journal      = {STAR Protocols},
  number       = {4},
  publisher    = {Elsevier},
  title        = {{Protocol for fabricating elastomeric stencils for patterned stem cell differentiation}},
  doi          = {10.1016/j.xpro.2024.103187},
  volume       = {5},
  year         = {2024},
}

@article{13136,
  abstract     = {Despite its fundamental importance for development, the question of how organs achieve their correct size and shape is poorly understood. This complex process requires coordination between the generation of cell mass and the morphogenetic mechanisms that sculpt tissues. These processes are regulated by morphogen signalling pathways and mechanical forces. Yet, in many systems, it is unclear how biochemical and mechanical signalling are quantitatively interpreted to determine the behaviours of individual cells and how they contribute to growth and morphogenesis at the tissue scale. In this review, we discuss the development of the vertebrate neural tube and somites as an example of the state of knowledge, as well as the challenges in understanding the mechanisms of tissue size control in vertebrate organogenesis. We highlight how the recent advances in stem cell differentiation and organoid approaches can be harnessed to provide new insights into this question.},
  author       = {Minchington, Thomas and Rus, Stefanie and Kicheva, Anna},
  issn         = {2452-3100},
  journal      = {Current Opinion in Systems Biology},
  publisher    = {Elsevier},
  title        = {{Control of tissue dimensions in the developing neural tube and somites}},
  doi          = {10.1016/j.coisb.2023.100459},
  volume       = {35},
  year         = {2023},
}

@article{12245,
  abstract     = {MicroRNAs (miRs) have an important role in tuning dynamic gene expression. However, the mechanism by which they are quantitatively controlled is unknown. We show that the amount of mature miR-9, a key regulator of neuronal development, increases during zebrafish neurogenesis in a sharp stepwise manner. We characterize the spatiotemporal profile of seven distinct microRNA primary transcripts (pri-mir)-9s that produce the same mature miR-9 and show that they are sequentially expressed during hindbrain neurogenesis. Expression of late-onset pri-mir-9-1 is added on to, rather than replacing, the expression of early onset pri-mir-9-4 and -9-5 in single cells. CRISPR/Cas9 mutation of the late-onset pri-mir-9-1 prevents the developmental increase of mature miR-9, reduces late neuronal differentiation and fails to downregulate Her6 at late stages. Mathematical modelling shows that an adaptive network containing Her6 is insensitive to linear increases in miR-9 but responds to stepwise increases of miR-9. We suggest that a sharp stepwise increase of mature miR-9 is created by sequential and additive temporal activation of distinct loci. This may be a strategy to overcome adaptation and facilitate a transition of Her6 to a new dynamic regime or steady state.},
  author       = {Soto, Ximena and Burton, Joshua and Manning, Cerys S. and Minchington, Thomas and Lea, Robert and Lee, Jessica and Kursawe, Jochen and Rattray, Magnus and Papalopulu, Nancy},
  issn         = {1477-9129},
  journal      = {Development},
  keywords     = {Developmental Biology, Molecular Biology},
  number       = {19},
  publisher    = {The Company of Biologists},
  title        = {{Sequential and additive expression of miR-9 precursors control timing of neurogenesis}},
  doi          = {10.1242/dev.200474},
  volume       = {149},
  year         = {2022},
}

@article{15262,
  abstract     = {The Hunchback (Hb) transcription factor is crucial for anterior-posterior patterning of the Drosophila embryo. The maternal hb mRNA acts as a paradigm for translational regulation due to its repression in the posterior of the embryo. However, little is known about the translatability of zygotically transcribed hb mRNAs. Here, we adapt the SunTag system, developed for imaging translation at single-mRNA resolution in tissue culture cells, to the Drosophila embryo to study the translation dynamics of zygotic hb mRNAs. Using single-molecule imaging in fixed and live embryos, we provide evidence for translational repression of zygotic SunTag-hb mRNAs. Whereas the proportion of SunTag-hb mRNAs translated is initially uniform, translation declines from the anterior over time until it becomes restricted to a posterior band in the expression domain. We discuss how regulated hb mRNA translation may help establish the sharp Hb expression boundary, which is a model for precision and noise during developmental patterning. Overall, our data show how use of the SunTag method on fixed and live embryos is a powerful combination for elucidating spatiotemporal regulation of mRNA translation in Drosophila.},
  author       = {Vinter, Daisy J. and Hoppe, Caroline and Minchington, Thomas and Sutcliffe, Catherine and Ashe, Hilary L.},
  issn         = {1477-9129},
  journal      = {Development},
  keywords     = {Developmental Biology, Molecular Biology},
  number       = {18},
  publisher    = {The Company of Biologists},
  title        = {{Dynamics of hunchback translation in real-time and at single-mRNA resolution in the Drosophila embryo}},
  doi          = {10.1242/dev.196121},
  volume       = {148},
  year         = {2021},
}