RESEARCH

Individuals of the same species can differ widely in size, but their organs have reproducible proportions and patterns of cell types. We are interested in the mechanisms that control tissue growth and pattern formation and ensure reproducible developmental outcomes. We study these mechanisms in the developing vertebrate neural tube.

The questions about size, reproducibility, patterns and dynamics that we ask are inherently quantitative, hence in our work we aim to obtain quantitative and dynamic data. To combine these data with mathematical modelling and theoretical descriptions, we have a mix of experimentalists and theorists in the group and we work in close collaboration with biophysicists.

Morphogen gradients and pattern formation

Our focus is on secreted signalling molecules, called morphogens. Morphogens forms gradients of activity across the tissue and influence both the specification of diverse cell types, and tissue growth. We found that in the neural tube, cells integrate information from the opposing morphogen gradients of Shh and BMP and this maximizes the precision of pattern formation (Zagorski et al, 2017).

In our current work, we are investigating further how is the dynamics of signalling gradients controlled, is there any cross-talk between the signalling gradients, how do cells interpret combinations of signalling inputs. We use mouse and chick to address these questions, as well as in vitro organoid systems.

A) A section through a mouse neural tube, expressing a Shh signalling reporter (green) and stained for pSmad1/5/8, a readout of BMP signalling (red). B) A set of signalling profiles that have been quantified from such images. C) Decoding map of the response to BMP and Shh in neural progenitors. The positional identities from ventral (blue) to dorsal (red) that cells adopt when exposed to different levels of BMP and Shh signaling are color coded.

Size and shape of the neural tube

The early stages of neural tube development are remarkable in that they involve rapid growth and profound morphogenetic changes in which the neural plate bends closes to form a neural tube. We found that during these early stages, the neural epithelium is in a fluid-like state and undergoes substantial cell rearrangements (Bocanegra et al, 2023). We also found that the declining growth rate over time leads to a decrease in the cell rearrangements. These changes in growth rate also affect the anisotropy of tissue growth (Guerrero et al, 2019) and thereby the shape of the tissue.

In our current work, we are investigating what are the mechanisms that control the growth rate, what is the role of morphogen signalling as well as mechanical forces in growth control.

EYFP labelled clones in the ventral portion of the mouse neural tube at E11.5. Clone size and shape differ between progenitor domains (Olig2, red; Nkx2.2 blue).

Grants