Multicellular organisms are formed by a large number of cell types, which serve as the components of tissues and organs. In the Simoes-Costa Lab, we study how cellular diversity arises during vertebrate embryonic development. We employ systems-level approaches to decode the molecular programs that drive changes in cell identity. Our research group is particularly interested in how gene regulatory networks operate in space to generate complex arrangements of cells.

Our model of choice is the neural crest, a stem cell population that plays a crucial role in the genesis of the vertebrate body plan. Neural crest cells emerge from the central nervous system to give rise to intricate structures like the craniofacial skeleton and the peripheral ganglia. They have served as an essential developmental model system due to their motility and ability to form various cell types. We approach the neural crest as a system for integrative biology, surveying how multiple layers of regulation work together to control cell identity and behavior. We are currently pursuing the following research topics:

Gene regulatory networks in embryonic development: Cellular diversity arises from the establishment of distinct molecular states in stem cell populations. We study how gene regulatory networks operate to transform cell identity to generate specialized tissues. Understanding the logic of these developmental programs will shed light on the control of cell state transitions and allow us to reprogram cell identity and behavior.

The spatial control of cell fate commitment: Tissues and organs have complex tridimensional structures, and their assembly relies upon the precise placement of cell types in space. As a result, differentiation must be coupled with the extracellular signals that pattern the early embryo. We are investigating how environmental information is processed by the genome to ensure cells differentiate at the right time and place.

Reactivation of developmental gene circuits in cancers: Occasionally, development gene circuits that should be silenced during differentiation are abnormally reactivated in adult cells. This may lead to the re-emergence of embryonic behaviors and initiate malignant transformation. We study the biology of neural crest derived cancers to understand how stem cell identity is coopted during tumorigenesis and metastasis.