The Sun Laboratory
Faculty Xin Sun
Xin Sun
Associate Professor, Department of Genetics
xsun@wisc.edu
Organ System/Disease Focus
Lung and Limb development and disease.
Aligned Research Focus
Organ progenitor/stem cell biology
Research Description
The long-term objective of my research program is to understand the initiation and maintenance of progenitors/stem cells in the context of intact organs. We use mouse genetic tools to address questions in two organs, the limb and the lung. The behavior of limb skeletal progenitors was first described approximately 40 years ago. Based on data from classical lineage labeling and transplantation experiments, it was proposed that cells within the distal mesenchyme of limb buds remain labile in fate until they leave this region. In the past few years, our findings have helped to define the precise role of signaling molecules, in particular fibroblast growth factors (FGFs), in maintaining progenitor characteristics in the limb bud. Our current focus is to use the collection of our mutants to identify the mechanisms downstream of signaling in this context.
Respiratory progenitors, giving rise to both the trachea and lung, arise from the ventral foregut endoderm. While digestive progenitors, giving rise to esophagus and stomach, emerge from the dorsal foregut endoderm. The choice of cell fates here are likely influenced by multiple signaling molecules as their pathways intersect in the foregut. Our genetic studies show that canonical WNT/ b-Catenin pathway and bone morphogenetic protein (BMP) pathway, both promote the identity of the respiratory lineage at the expense of the digestive lineage. Our current work is focused on using the foregut as an in vivo setting to dissect the crosstalk among signaling pathways in establishing internal organ progenitors.
Selected References
Verheyden, J.M. and Sun, X. (2008) An Fgf/Gremlin Inhibitory feedback loop triggers termination of limb bud outgrowth. Nature 454, 638-641. http://www.nature.com/nature/journal/v454/n7204/full/nature07085.html
Zhang, Z., Verheyden, J.M. and Sun, X. (2009) FGF-regulated Etv genes are essential for repressing Shh expression in mouse limb buds. Developmental Cell 16, 607-613. http://www.cell.com/developmental-cell/retrieve/pii/S1534580709000823
Harris-Johnson, K.S., Domyan, E.T., Vezina, C.M. and Sun, X. (2009) b-Catenin promotes respiratory progenitor identity in mouse foregut. PNAS 106(38), 16287-92. http://www.pnas.org/content/106/38/16287.long
Domyan, E.T., Ferretti, E., Throckmorton, K., Mishina, Y., Nicolis, S.K. and Sun, X. (2011) Signaling through BMP receptors promotes respiratory identity in the foregut via repression of Sox2. Development 138(5): 971-981. http://www.ncbi.nlm.nih.gov/pubmed/21303850
Zhang Z, O'Rourke JR, McManus MT, Lewandoski M, Harfe BD and Sun X.(2011) The microRNA-processing enzyme Dicer is dispensable for somite segmentation but essential for limb bud positioning. Developmental Biology 351(2):254-265. http://www.ncbi.nlm.nih.gov/pubmed/21256124