Children's National Medical Center Principal Investigator, Children's Research Institute (CRI), Center for Neuroscience Research (CNR) George Washington University School of Medicine and Health Sciences Assistant Professor, Pediatrics

Research Interests

Laboratory Members:
Anjali Angelika Sarkar – Postdoctoral Fellow

The Zohn Lab is currently recruiting highly motivated Postdoctoral Fellows and Research Technicians. For more information please send CV via e-mail to izohn@cnmcresearch.org

Our goal is to understand the genes and signal transduction pathways required for morphogenesis of the vertebrate embryo. We use a forward genetic approach in the mouse to identify novel genes required for two early morphogenic events: gastrulation and neural tube closure. From this screen we have identified a number of mouse mutants. The current focus of the lab is on the characterization of the genetic and developmental defects in two ENU-derived mutant mouse lines that display defects in gastrulation and neural tube closure: droopy eye (drey) and openmind (opm).

We use a variety of techniques to characterize the developmental defects in these mutant mice strains including, embryology, molecular biology, biochemistry, genetics and genetic engineering.

Gastrulation:
During development of the mouse embryo, gastrulation results in the formation of the three definitive germ layers and establishment of the embryonic body plan. The mouse gastrula (Figure 3) consists of a cup-like structure (the epiblast) nestled within the visceral endoderm. Mesoderm cells undergo an epitheilial to mesenchymal transition (EMT) and migrate away from the primitive streak. This EMT is mediated by the change in expression of a number of cell adhesion molecules, one of the most important being Ecadherin. Through our analysis of the drey mouse mutant line, we have uncovered a novel p38 MAPK-dependent pathway that mediates the downregulation of Ecadherin protein (Zohn et al 2006, and Figure 4). Current experiments address how p38 activity regulates E-cadherin expression; how the interaction of p38IP with p38 MAPK the identity of the upstream signals that regulate p38 activation in the primitive streak.

Neural Tube Closure:
In humans, neural tube defects (NTDs), including anencephaly/exencephaly and spina bifida, are among the most common birth defects, yet the etiologies of these defects remain poorly understood (reviewed in (Zohn et al., 2005). Disruption of multiple developmental pathways including defects in embryonic patterning of the mesoderm, neural crest and neural tissue or defects in cell movement, growth and death can all result in a failure to close the neural tube, thus making neural tube closure an extremely sensitive readout of a wide variety of defects in early mouse development. Further analysis of mouse mutants displaying NTDs will continue to deepen our understanding of the pathways that control morphogenesis of the vertebrate embryo.

Current studies utilize the drey and opm mutant mouse lines to further our understanding of the genetic and signal transduction pathways that regulate neural tube closure.

Both drey and opm are required for proper development of the head mesenchyme, a tissue that is essential for proper cranial neural tube closure. The headmesenchyme is derived from both cranial neural crest and mesoderm. Using a combination of genetic, molecular and biochemical approaches we are further exploring the signal transduction and developmental genetic pathways that these genes regulate.

Publications