Model organisms are a powerful genetic tool for identifying and investigating genes that contribute to heritable disorders.  Our laboratory is using genetic and developmental approaches in mouse disease models to identify and characterize genes that contribute to congenital disorders of the autonomic nervous system.  Our initial efforts have focused on development of the enteric branch of the autonomic system.  The enteric nervous system (ENS) controls motility, mucosal transport, tissue defense and vascular perfusion of the gastrointestinal tract.  Abnormalities of this system give rise to functional gastrointestinal disorders like Hirschsprung disease (HSCR) and neuronal intestinal dysplasia.  We are utilizing the mouse mutant Sox10Dom to map genes that modifiy the severity of defects in the ENS of these mice.  Concurrent with our genetic analysis of the Sox10 mutants we are taking embryological approaches to investigate the mechanism of action of the Sox10 modifier loci before the genes are identified.  The effects of distinct genetic backgrounds as well as interacting alleles and mutations are being investigated during development.  To complement our analyses of disease models, the laboratory is investigating the normal developmental processes of ENS formation.  Transgenic strategies that rely upon expression of green flourescent protein are being implemented to facilitate monitoring, selection and gene expression analysis in the ENS during ontogeny of the gastrointestinal tract.This is default text for the community description. This community's Chief or Leader(s) can modify it by editing this page.


Featured publications

  1. A Uchl1-Histone2BmCherry:GFP-gpi BAC transgene for imaging neuronal progenitors. Wiese CB, Fleming N, Buehler DP, Southard-Smith EM (2013) Genesis 51(12): 852-61
    › Primary publication · 24123561 (PubMed) · PMC3953494 (PubMed Central)
  2. A genome-wide screen to identify transcription factors expressed in pelvic Ganglia of the lower urinary tract. Wiese CB, Ireland S, Fleming NL, Yu J, Valerius MT, Georgas K, Chiu HS, Brennan J, Armstrong J, Little MH, McMahon AP, Southard-Smith EM (2012) Front Neurosci : 130
    › Primary publication · 22988430 (PubMed) · PMC3439845 (PubMed Central)
  3. An optimized procedure for fluorescence-activated cell sorting (FACS) isolation of autonomic neural progenitors from visceral organs of fetal mice. Buehler DP, Buehler D, Wiese CB, Wiese C, Skelton SB, Southard-Smith EM, Southard-Smith M (2012) J Vis Exp (66): e4188
    › Primary publication · 22929412 (PubMed) · PMC3671830 (PubMed Central)
  4. Enteric nervous system specific deletion of Foxd3 disrupts glial cell differentiation and activates compensatory enteric progenitors. Mundell NA, Plank JL, LeGrone AW, Frist AY, Zhu L, Shin MK, Southard-Smith EM, Labosky PA (2012) Dev Biol 363(2): 373-87
    › Primary publication · 22266424 (PubMed) · PMC3288190 (PubMed Central)
  5. The GUDMAP database--an online resource for genitourinary research. Harding SD, Armit C, Armstrong J, Brennan J, Cheng Y, Haggarty B, Houghton D, Lloyd-MacGilp S, Pi X, Roochun Y, Sharghi M, Tindal C, McMahon AP, Gottesman B, Little MH, Georgas K, Aronow BJ, Potter SS, Brunskill EW, Southard-Smith EM, Mendelsohn C, Baldock RA, Davies JA, Davidson D (2011) Development 138(13): 2845-53
    › Primary publication · 21652655 (PubMed) · PMC3188593 (PubMed Central)
  6. Isolation and live imaging of enteric progenitors based on Sox10-Histone2BVenus transgene expression. Corpening JC, Deal KK, Cantrell VA, Skelton SB, Buehler DP, Southard-Smith EM (2011) Genesis 49(7): 599-618
    › Primary publication · 21504042 (PubMed) · PMC3212811 (PubMed Central)
  7. Genetic background impacts developmental potential of enteric neural crest-derived progenitors in the Sox10Dom model of Hirschsprung disease. Walters LC, Cantrell VA, Weller KP, Mosher JT, Southard-Smith EM (2010) Hum Mol Genet 19(22): 4353-72
    › Primary publication · 20739296 (PubMed) · PMC2957318 (PubMed Central)
  8. A Histone2BCerulean BAC transgene identifies differential expression of Phox2b in migrating enteric neural crest derivatives and enteric glia. Corpening JC, Cantrell VA, Deal KK, Southard-Smith EM (2008) Dev Dyn 237(4): 1119-32
    › Primary publication · 18351668 (PubMed) · PMC3093109 (PubMed Central)
  9. Fate mapping using Cited1-CreERT2 mice demonstrates that the cap mesenchyme contains self-renewing progenitor cells and gives rise exclusively to nephronic epithelia. Boyle S, Misfeldt A, Chandler KJ, Deal KK, Southard-Smith EM, Mortlock DP, Baldwin HS, de Caestecker M (2008) Dev Biol 313(1): 234-45
    › Primary publication · 18061157 (PubMed) · PMC2699557 (PubMed Central)
  10. Relevance of BAC transgene copy number in mice: transgene copy number variation across multiple transgenic lines and correlations with transgene integrity and expression. Chandler KJ, Chandler RL, Broeckelmann EM, Hou Y, Southard-Smith EM, Mortlock DP (2007) Mamm Genome 18(10): 693-708
    › Primary publication · 17882484 (PubMed) · PMC3110064 (PubMed Central)

Community Leaders

Contact Information

2215-B Garland Ave
1175 Light Hall
Nashville, TN 37027
United States
615-936-2174 (p)

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Keywords & MeSH Terms

MeSH terms are retrieved from PubMed records. Learn more.

Key: MeSH Term Keyword

Alleles autonomic nervous system developmental biology Embryo, Mammalian Endothelins enteric nervous system Female Gene Order Genes, Dominant genetics genomics Homeodomain Proteins Humans Male Molecular Imaging mouse disease models neural crest development Neural Stem Cells Neuroglia Neurons Nuclear Proteins Quantitative Trait Loci quantitative trait loci Receptor, Endothelin B Reverse Transcriptase Polymerase Chain Reaction SOXE Transcription Factors transcription factor Transgenes X Chromosome