ayout 1 - EMBL Grenoble

Developmental Biology Unit
The development of living organisms requires the integration and precise coordination of all basic cellular and molecular processes
in space and time. Live organisms are the physical manifestation of complex regulatory networks interacting with their environment.
Research in the Developmental Biology Unit is aimed at elucidating the basic principles and mechanisms underlying fundamental
developmental processes, such as cell fate-specification and polarity, tissue morphogenesis, organogenesis and growth control. A
major goal is to understand the regulatory cascades – hierarchies of gene expression choices – that control developmental decisions.
Using selected animal and plant model organisms, our groups combine genetics, biochemistry, bioinformatics, high-throughput genomics,
proteomics, and imaging to understand how cellular and molecular processes evolved and are coordinated in living organisms.
Cell polarity underlies many fundamental decisions in development, both in plants and animals. In many organisms, the first developmental
events occur before the onset of zygotic transcription, under the control of by mRNAs and proteins asymmetrically localised
in the egg cell. Understanding the mechanisms underlying cell polarisation, mRNA localisation and
translational control in Drosophila development is a topic of research in the unit. Understanding the polarised
transport of auxin in plants, which determines the positioning of lateral organs, such as leaves and flowers,
and how this molecule specifies different cell types is also topic of research.
During development, progenitor cells are amplified and differentiate into tissues of characteristic
shape and function. The expression of many differentiation factors is required for these morphological
changes. Research in the unit aims to elucidate how cells in the early Drosophila embryo reorganize
their content in response to the expression of key developmental transcription factors
and, specifically, how tissue-specific gene expression controls patterns of protein and membrane
trafficking, and how this trafficking regulates cell fate and behaviour.
Elucidating the temporal organisation, or timing, of embryonic development is another aim
of research in the unit. Using the mouse model, the mechanisms controlling overall developmental
rate at an organismal level, as well as the timing of individual patterning processes,
including the dynamics of underlying signaling pathways, are being investigated. Analysis of
novel mouse reporter lines using real-time imaging techniques allows visualisation of the activity
and dynamics of signalling pathways over time, in the context of a developing embryo.
The marine annelid Platynereis is an ideal model for exploring the evolution of cell types, through
large-scale expression profiling at cellular resolution and dissection of gene regulatory networks,
and has already allowed elucidation of the evolutionary origin of the vertebrate hypothalamus. Research
in the unit also aims to solve one of the remaining big mysteries in animal evolution: the evolution
of the central nervous system (CNS).
Several groups in the unit seek to understand both normal development and its deviations in disease.
During brain development, vast numbers of neurons are targeted for death and are cleared
rapidly and efficiently by a resident lineage of phagocytes, the microglia. Most CNS pathologies are
accompanied by activation of the phagocytic microglia, highlighting the importance of understanding
the mechanisms underlying the function of these cells, both in healthy and diseased brains.
Using advanced in vivo imaging combined with genetic approaches, the dynamic relationship between
neurons and microglia in zebrafish is actively investigated.
Re-shuffling of regulatory inputs after chromosomal rearrangements is the likely cause of several
human genetic disorders and may also link large structural variations widespread in humans to modulation
of the quantitative, tissue-specific and temporal expression patterns of neighbouring genes.
With a focus on the regulatory architecture of several developmental loci, understanding the molecular
mechanisms that control functional interactions between genes and remote cis-regulatory elements
and determining how they contribute to phenotypic variations during vertebrate evolution and
in humans is an aim of research in the unit.
The unit’s research has also led to development of mouse models for endocrine cancer, premature ovarian
failure, polycystic kidney disease and obesity. The combination of genetics, expression profiling and proteomics
is providing important insight into the molecular basis of these diseases and of their normal developmental
counterparts.
Anne Ephrussi
Coordinator, Developmental Biology Unit