The Labosky Lab is interested in studying the gene regulatory networks (GRNs) that control normal development of the mammalian embryo and regulate the fate of embryonic progenitor cells. Their long-term goal is to understand stem cell properties of both embryonic stem cells (ESCs) and neural crest stem cells (NCSCs) in order to precisely regulate their differentiation and self-renewal.
One approach to defining the GRNs controlling stem cell properties is to discover key proteins functioning at decision points in the network and lab members have done this with their functional characterizations of the transcription factor Foxd3. Foxd3 is expressed in multiple disparate stem/progenitor cell types both in vivo and in vitro. In addition, this protein is indispensible for maintained self-renewal properties and potency of stem cells. In the neural crest, removal of Foxd3 biases the lineage choice of this multipotent cell type with an overall increase in the progenitors that take on a mesenchymal/myofibroblast/smooth muscle cell fate versus a neural cell fate. The lab is using this knowledge and multiple mouse models and ESC models that they have generated as an access point into the GRNs controlling self-renewal and multi/pluripotency of both ESCs and NCSCs. Their work will define conserved and novel mechanisms in ESCs and NCSCs leading to robust directed differentiation models for NCSCs, an accessible postnatal murine and human multipotent stem cell type.