Our lab uses molecular genetic tools to
study the reproduction and development of
a variety of organisms, from mice to sharks.
Currently, work in the lab is focused on four
unique 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 copy of each
gene from their mother and one copy from their
father, and most genes are expressed equivalently
from each copy. A group of ~100 genes defies
this rule, however, being expressed from only
one of the two parental alleles. These are
the imprinted genes, and the process that
regulates their parental-specific expression
is called genomic imprinting. Imprinted genes
play important roles in mammalian growth and
development, and their deregulation underlies
many human congenital diseases and is involved
in the etiology of cancer. The mouse, Mus
musculus, is being used as a model system
to investigate the developmental functions
of imprinted genes, and to identify the mechanisms
that regulate genomic imprinting.
A mouse model for congenital hydrocephalus.
Congenital hydrocephalus, the accumulation
of excess cerebrospinal fluid (CSF) in the
ventricles of the brain, is the most common
human neurodevelopmental disorder. This disease
occurs in 1 in every 500 children, and if
left untreated causes increasing neurological
damage that leads to cognitive and motor defects.
Our lab has developed a mouse model for juvenile
hydrocephalus (Jh mice). These mice develop
hydrocephalus by 2 weeks of age, and results
from the mutation of a single novel gene whose
function is unknown. We are using a combination
of molecular, biochemical and microscopic
techniques to characterize the neural defects
of Jh mice, and to understand the normal function
of the Jh gene.
A novel gene expressed in the developing
mammalian limb. The developing mouse
limb forms initially 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 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
early expression 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). The
whale shark is the largest shark and the largest
fish, reaching lengths of 45 feet or more.
They are planktivorous filter-feeders who
get their name from their large size and method
of feeding. Whale sharks are open ocean animals,
but gather in large feeding aggregations in
certain parts of the world at predictable
times. A key question for both the biology
and conservation of whale sharks is whether
these aggregations represent isolated breeding
populations of animals, or whether whale sharks
are migratory and composed of a single global
population. As active fisheries exist for
whale sharks in many countries, their migratory
patterns can determine the risks they face.
We are using genetic analysis to understand
the genetic relatedness of whale sharks found
in different parts of the world.