Stem cells in the genomic age

A report on the 2006 Joint Spring Meeting of the British Society for Developmental Biology and the British Society for Cell Biology, York, UK, 20-23 March 2006

Pax6 mutant cerebral organoids partially recapitulate phenotypes of Pax6 mutant mouse strains

Cerebral organoids show great promise as tools to unravel the complex mechanisms by which the mammalian brain develops during embryogenesis. We generated mouse cerebral organoids harbouring constitutive or conditional mutations in Pax6, which encodes a transcription factor with multiple important roles in brain development. By comparing the phenotypes of mutant organoids with the well-described phenotypes of Pax6 mutant mouse embryos, we evaluated the extent to which cerebral organoids reproduce phenotypes previously described in vivo. Organoids lacking Pax6 showed multiple phenotypes associated with its activity in mice, including precocious neural differentiation, altered cell cycle and an increase in abventricular mitoses. Neural progenitors in both Pax6 mutant and wild type control organoids cycled more slowly than their in vivo counterparts, but nonetheless we were able to identify clear changes to cell cycle attributable to the absence of Pax6. Our findings support the value of cerebral organoids as tools to explore mechanisms of brain development, complementing the use of mouse models

Enabling neighbour-labelling: using synthetic biology to explore how cells influence their neighbours

Cell-cell interactions are central to development, but exploring how a change in any given cell relates to changes in the neighbour of that cell can be technically challenging. Here, we review recent developments in synthetic biology and image analysis that are helping overcome this problem. We highlight the opportunities presented by these advances and discuss opportunities and limitations in applying them to developmental model systems

Biotic analogies for self-organising cities

Nature has inspired generations of urban designers and planners in pursuit of harmonious and functional built environments. Research regarding self-organisation has encouraged urbanists to consider the role of bottom-up approaches in generating urban order. However, the extent to which self-organisation-inspired approaches draw directly from nature is not always clear. Here, we examined the biological basis of urban research, focusing on self-organisation. We conducted a systematic literature search of self-organisation in urban design and biology, mapped the relationship between key biological terms across the two fields and assessed the quality and validity of biological comparisons in the urban design literature. Finding deep inconsistencies in the mapping of central terms between the two fields, a preponderance for cross-level analogies and comparisons that spanned molecules to ecosystems, we developed a biotic framework to visualise the analogical space and elucidate areas where new inspiration may be sought

SyNPL:Synthetic notch pluripotent cell lines to monitor and manipulate cell interactions in vitro and in vivo

Cell-cell interactions govern differentiation and cell competition in pluripotent cells during early development, but the investigation of such processes is hindered by a lack of efficient analysis tools. Here, we introduce SyNPL: clonal pluripotent stem cell lines that employ optimised Synthetic Notch (SynNotch) technology to report cell-cell interactions between engineered ‘sender’ and ‘receiver’ cells in cultured pluripotent cells and chimaeric mouse embryos. A modular design makes it straightforward to adapt the system for programming differentiation decisions non-cell-autonomously in receiver cells in response to direct contact with sender cells. We demonstrate the utility of this system by enforcing neuronal differentiation at the boundary between two cell populations. In summary, we provide a new adaptation of SynNotch technology that could be used to identify cell interactions and to profile changes in gene or protein expression that result from direct cell-cell contact with defined cell populations in culture and in early embryos, and that can be customised to generate synthetic patterning of cell fate decisions