Transcriptional targets of Foxd3 in murine ES cells

• Foxd3 regulates expression of genes controlling developmental processes.
• Foxd3 both positively and negatively regulates expression of downstream genes.
• Novel direct targets of Foxd3 include: Sox4, Safb, Sox15, Fosb, Pmaip1, and Smarcd3.
• Foxd3 functions upstream of genes required for skeletal muscle development.

Understanding gene regulatory networks controlling properties of pluripotent stem cells will facilitate development of stem cell-based therapies. The transcription factor Foxd3 is critical for maintenance of self-renewal, survival, and pluripotency in murine embryonic stem cells (ESCs). Using a conditional deletion of Foxd3 followed by gene expression analyses, we demonstrate that genes required for several developmental processes including embryonic organ development, epithelium development, and epithelial differentiation were misregulated in the absence of Foxd3. Additionally, we identified 6 novel targets of Foxd3 (Sox4, Safb, Sox15, Fosb, Pmaip1 and Smarcd3). Finally, we present data suggesting that Foxd3 functions upstream of genes required for skeletal muscle development. Together, this work provides further evidence that Foxd3 is a critical regulator of murine development through the regulation of lineage specific differentiation.