Mechanisms Underlying Mammalian Development and Birth Defects

My research uses genetically engineered mice as a model system to understand the mechanisms underlying cell lineage determination and embryo patterning during mammalian development. My major focus has been on the role of the Lhx1 gene. Lhx1 encodes an evolutionarily conserved transcription factor expressed in the gastrula organizer region of the mouse embryo. The gastrula organizer is important in the specification of the embryonic germ layers and in the establishment of the basic body plan of the embryo. Lhx1-deficient mice created by gene targeting in embryonic stem cells lack heads and mice with reduced Lhx1 activity display craniofacial birth defects. These malformations are due in part to a defect in the formation of prechordal endoderm, a tissue that underlies the presumptive forebrain region during early fetal development. My current work focuses on understanding the genetic regulatory network that Lhx1 directs during prechordal endoderm formation, defining its effect on cell behavior and determining the extent to which teratogens affect the Lhx1 pathway.

Selected Publications

Shawlot, W. and Behringer, R.R. (1995). Requirement for Lim1 in head organizer function. Nature, 374, 425-430.

Shawlot, W., Deng, J.M. and Behringer, R.R. (1998). Expression of the mouse cerberus-related gene, Cerr1, suggests a role in anterior neural induction and somitogenesis. Proc. Natl. Acad. Sci. USA, 95, 6198-6203.

Shawlot, W., Wakamiya, M., Kwan, K.M., Kania, A., Jessell, T.M. and Behringer, R.R. (1999). Lim1 is required in both the primitive streak-derived tissues and visceral endoderm for head formation in the mouse. Development, 126, 4925-4932.

Perea-Gomez Aitana, Vella, D.D.J., Shawlot, W., Oulad-Abdelghani, M., Chazaud, C., Meno, C., Pfister, V., Chen, L., Robertson, E, Hamada, H., Behringer, R.R. and Ang, S.-L. (2002). Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks. Dev. Cell, 3, 745-756.

Kobayashi, A, Shawlot, W., Kania, A. and Behringer, R.R. (2004). Requirement of Lim1 for female reproductive tract development. Development 131: 539-549.

Petryk, A., Anderson, R.M., Jarcho, M.J., Leaf, I., Carlson, C.S., Klingensmith, J., Shawlot, W. and O'Connor, M. (2004). The mammalian twisted gastrulation gene functions in foregut and craniofacial development. Dev. Biol. 267: 374-386.

Yamamoto, M., Saijoh, Y., Perea-Gomez, A., Shawlot, W., Behringer, R.R., Ang, S.-L. Hamada, H. and Meno, C. (2004). Nodal antagonists regulate migration of the visceral endoderm along the future anteroposterior axis of the mouse embryo. Nature 428: 387-392.

Nishioka, N., Nagano, S., Nakayama, R., Kiyonari, H., Ijiri, T., Taniguchi, K., Shawlot, W., Hayashizaki, Y., Westphal, H., Behringer, R.R. Matsuda, Y., Sakoda, S., Kondoh, H. and Sasaki, H. (2005). Ssdp1 regulates head morphogenesis of mouse embryos by activating the Lim1-Ldb1 complex. Development 132, 2535-2546.

Pedersen, A, Skjong, C. and Shawlot, W. (2005). Lim1 is required for nephric duct extension and ureteric bud morphogenesis. Dev Biol. 288, 571-581.

Shawlot, W., Vazquez-Chantada, M., Wallingford, JB. and Finnell, RH. (2015). Rfx2 is required for spermatogenesis in the mouse. Genesis 9, 604-611.