The Southard-Smith Laboratory uses genetic and embryological approaches in the mouse to identify genes that influence processes of NC commitment, migration and differentiation in the enteric nervous system (ENS). Lab members have identified genome intervals for multiple modifier loci that alter the severity and penetrance of aganglionosis in the Sox10Dom mouse model of Hirschsprung disease. In addition, the Southard-Smith lab has undertaken transgene approaches to study divergence of neurons and glia during normal ENS development. Regulatory regions of lineage specific genes have been linked to nuclear-localized fluorescent reporters and are being applied to investigate the timing and transcriptional control of cell lineage divergence in the neural crest stem cells that populate the gastrointestinal tract during development. Trainees in the lab analyze enteric neural crest differentiation and migration using a combination of immunohistochemistry, transgenic reporters and confocal imaging. Genetic effects of modifiers on enteric neural crest migration are evaluated in congenic lines of mice by similar methods.

RECENT PUBLICATIONS

A Histone2BCerulean BAC transgene identifies differential expression of Phox2b in migrating enteric neural crest derivatives and enteric glia. 
2008 Developmental Dynamics 237; 1119-1132

Fate mapping using Cited1-CreERT2 mice demonstrates that the cap mesenchyme contains self-renewing progenitor cells and gives rise exclusively to nephronic epithelia. 
2008 Developmental Biology 313: 234-245