A long-standing goal of developmental biology is to understand how multiple cell types are generated and maintained in highly organized spatial patterns. Our group explores the mechanisms underlying the organization of cells into highly developed structures in the Nervous System, with special attention to the patterning of cell lineages.

The Central Nervous System is initially subdivided into regions with distinct identity that underlies the generation of a specific set of cell types, each of which must arise at the right time and place and in the correct proportions for normal development and function. We focus our studies on the embryonic development of the hindbrain, as a model to study how cellular compartments operate during brain development, and how cell diversity is generated. Our goals are to unveil when and how brain progenitors commit to a given fate, how they behave once committed, and how cell fate decisions are regulated to generate the distinct cell lineages. We use zebrafish embryos as model system because permits functional genetic studies to be combined with 3D+time in vivo imaging.

If you are interested you can read more about our projects below:


The generation of cell lineage trees

We generated the complete lineage tree of the neurosensory elements of the inner ear and of different hindbrain progenitor populations by high spatial and temporal resolution imaging. Our approach uniquely allows to quantitatively and simultaneously studying progenitor cells in their native/modified environment such as progeny number, location and differentiation status. We provide dynamic maps of progenitor pools in the whole organ context, and correlate the progenitor potentials to the temporal and spatial gene requirements [Dyballa et al, 2017]. Now we want to apply our know how to more complex structures such as the hindbrain.

Fig 3


Deciphering how cell diversity is generated in the developing hindbrain

Another main goal is to explore the patterning of cell lineages within the hindbrain, and understand how cell fate decisions result in particular cell behavior within the rhombomeric regions and in the boundary cell population (BCP). We want to understand how the neurogenic/gliogenic capacity is allocated to specific territories combining high-resolution in vivo imaging and gene transcriptional activation signature analyses.

Fig 2


Understanding morphomechanics during hindbrain segmentation

Our aim is to study the impact of morphomechanical changes on tissue subdivision and cell organization within the hindbrain. Actomyosin cables act downstream of EphA/Ephrin signaling in the segregation of rhombomeric cell populations to avoid cell intermingling between different neuronal types [Calzolari et al 2014]. We are currently exploring the cellular machinery and the molecular players responsible of the assembly of the mechanical barrier.



Developing the digital Z-Hindbrain

Our aim is to build an expandable open-source atlas containing data from labels of molecular gene expression, cell identity, cell behavior and tissue growth information over time. This will provide a dynamic morphogenetic map allowing us to better understand how cell lineages are built up and how neuronal progenitors behave upon morphogenesis, an important challenge in neurobiology.