Introduction

In spite of the great advances of developmental biology, the mechanisms underlying morphogenesis and homeostasis of adult organs remain only superficially understood. Somatic stem cells are critical players during developmental growth and for maintaining adult tissue homeostasis; how these cells coordinate morphogenetic cues and fate specification during development is a fundamental question at the basis of tissue formation. However, the lack of a model enabling single cell and 4D resolution methods in vivo has been a major limitation to address this issue. In the lab, we study how stem cells engage in differentiation while retaining self-renewal potential and plasticity. We wish to define the signals controlling adult stem cell homeostasis and lineage specification, with the final goal of gaining mechanistic insights into organ morphogenesis, and also into the critical steps of malignant transformation. Our overarching goal is to explore the links between the molecular networks dictating cell fate and cellular behaviour during tissue morphogenesis.

Projects and Achievements

Our recent findings on embryonic mouse mammary gland led us to exploit this system as an ideal model to study spatial and temporal integration of stem cell commitment. We found that mammary stem cells engage into a unipotent cell fate during a narrow developmental window that coincides with the initial branching events that generate the mammary tree. We hypothesize that the same mechanisms controlling the switch from multipotency to unipotency in embryogenesis also maintain cell plasticity in adult committed cells. 

We combine in vivo genetic barcode lineage tracing tools coupled with single cell analyses, time-lapse of branching morphogenesis, modelling of clonal dynamics and functional studies in mouse mutants, to address the following fundamental questions: i) Which signals determine cell identity and potency during mammary development? ii) How is cell fate commitment coordinated with branching morphogenesis? iii) Are signal oscillations involved in differentiation, instructing tissue patterning during embryonic mammogenesis? iv) Are the molecular signals driving cell differentiation during organogenesis recapitulated by adult cells upon lineage conversion?

Impact

Our research projects are aimed at uncovering the molecular circuitries driving mammary gland development and the underlying mechanisms linking specific stem cell states to cell dynamics during tissue morphogenesis, fundamentally advancing our understanding of how organs are formed during development.

More generally, we intend to gain insights into the molecular control of adult stem cell maintenance, as well as into the mechanisms by which Notch signaling controls cell plasticity in both normal and pathological conditions.