About Dr. Schmidt's research
Our lab uses molecular genetics to study the reproduction and development of organisms ranging from mice to sharks. Current work in the lab is focused on four areas of study - the epigenetic control of mammalian development, mammalian brain development and neurodevelopmental disorders, mammalian limb development, and the population genetics of sharks.
Regulation of genomic imprinting.
Mammalian organisms inherit one allele of each gene from their mother and one from their father, and most genes are expressed equivalently from both alleles. A group of ~100 genes defies this rule, and are expressed from only one of the two parental alleles. These are imprinted genes, and the process that regulates their expression is called genomic imprinting. Imprinted genes play important roles in mammalian growth and
development, and their deregulation underlies many human diseases. Our lab is using the mouse as a model system to investigate the developmental functions of imprinted genes, and the mechanisms that regulate genomic imprinting.
A mouse model for congenital hydrocephalus.
Congenital hydrocephalus, the accumulation of excess fluid in the ventricles of the brain, is a common human neurodevelopmental disorder. Left untreated, this disease causes increasing neurological damage that leads to cognitive and motor defects. Our lab has developed a mouse model for juvenile hydrocephalus (Jhy
mice). These mice carry a mutation in a novel gene of unknown function, and they develop rapidly
progressing hydrocephalus by 2 weeks of age. We are using a combination of molecular, biochemical and microscopic techniques to characterize the neural defects of Jhy
mice, and to understand the function of the mutated gene.
A novel gene expressed in the developing mammalian limb.
The developing limb begins as the limb bud, a flattened "paddle" of tissue. Subsequently, cartilage rays appear that delineate the developing digits, and the interdigital mesenchyme (IDM) tissue joining the digits undergoes apoptosis. Our lab is studying a mouse gene trap integration that is expressed in the presumptive IDM early in limb development. There is evidence that the IDM specifies digit identity, and the pattern of this gene suggests that it may be involved in digit specification. We are using a combination of gene expression analysis and transgenic mice to identify the trapped gene and determine its function.
Population and reproductive genetics in the whale shark (Rhincodon typus).
Whale sharks are the largest fish in the ocean, reaching lengths of 40 feet or more. Though normally pelagic animals, whale sharks are seen in large feeding aggregations in certain parts of the world. The decreasing number and size of whale sharks at some aggregations suggests the species may be declining. A key question for whale shark conservation is whether these aggregations represent isolated populations, or whether whale sharks are migratory and comprise a single global population. Active fisheries exist for whale sharks in some countries, so their migratory patterns determine the risks they face. We are using genetic analysis to understand the relatedness of whale sharks on a global scale.
Appelbe, OK, Bollman, B, Attarwala, A, Triebes, LA, Muniz-Talavera, H,
Curry, DJ and Schmidt, JV. (2013) Disruption of the mouse Jhy gene causes
abnormal ciliary microtubule patterning and juvenile hydrocephalus.
Developmental Biology, 382:172-185.
Appelbe OK, Yevtodiyenko A, Muniz-Talavera H and Schmidt JV. (2013) Conditional
deletions refine the embryonic requirement for Dlk1. Mechanisms of
McMurray EN, Schmidt JV. (2012) Identification of imprinting regulators at
the Meg3 differentially methylated region. Genomics, 100:184-194.
Rogers ED, Ramalie JR, McMurray EN, Schmidt JV. (2012) Localizing
transcriptional regulatory elements at the mouse Dlk1 locus. PLoS One
Schmidt, JV, Chien, C-C, Sheikh, SI, Meekan, MG, Norman, BM and Joung, S-J.
(2010) Paternity analysis in a litter of whale shark embryos. Endangered
Species Research, 12:117-124.
McMurray EN, Rogers ED, Schmidt JV. (2009) Imprinting analysis in the
Acrodysplasia region of mouse chromosome 12. Bioscience Reports, 30:119-124.
Schmidt JV, Schmidt CL, Ozer F, Ernst RE, Feldheim KA, Ashley MV, Levine M.
(2009) Low genetic differentiation across three major ocean populations of
the whale shark, Rhincodon typus. PLoS One, 4:e4988.