A5041948504- Developmental Biology and Gene Regulation
- Hedgehog Signaling Pathway Studies
- Neurogenesis and neuroplasticity mechanisms
- Congenital heart defects research
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Animal Genetics and Reproduction
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Fetal and Pediatric Neurological Disorders
- Virus-based gene therapy research
- Glioma Diagnosis and Treatment
- Neonatal and fetal brain pathology
- Craniofacial Disorders and Treatments
- MicroRNA in disease regulation
- Genetics and Neurodevelopmental Disorders
- Cancer-related molecular mechanisms research
- Wnt/β-catenin signaling in development and cancer
- Single-cell and spatial transcriptomics
- Neuroinflammation and Neurodegeneration Mechanisms
- Renal and related cancers
- RNA regulation and disease
- Cancer-related gene regulation
- Vestibular and auditory disorders
Kettering University
2016-2025
Cornell University
2016-2025
Memorial Sloan Kettering Cancer Center
2014-2024
Harvard University
1999-2020
National Institutes of Health
1998-2020
Yale University
2020
Rockefeller University
2020
Brigham and Women's Hospital
2020
Princeton University
2020
Federation of American Societies for Experimental Biology
2020
Huntington's disease (HD) is a dominant neurodegenerative disorder caused by expansion of CAG repeat in the gene encoding huntingtin, protein unknown function. To distinguish between "loss function" and "gain models HD, murine HD homolog Hdh was inactivated targeting. Mice heterozygous for inactivation were phenotypically normal, whereas homozygosity resulted embryonic death. Homozygotes displayed abnormal gastrulation at day 7.5 resorbing 8.5. Thus, huntingtin critical early development,...
ABSTRACT The secreted factor Sonic hedgehog (SHH) is both required for and sufficient to induce multiple developmental processes, including ventralization of the CNS, branching morphogenesis lungs anteroposterior patterning limbs. Based on analogy Drosophila Hh pathway, GLI transcription factors in vertebrates are likely transduce SHH signaling repress Shh transcription. In order discriminate between overlapping versus unique requirements three Gli genes mice, we have produced a Gli1 mutant...
The Shh signaling pathway is required in many mammalian tissues for embryonic patterning, cell proliferation and differentiation. In addition, inappropriate activation of the has been implicated human tumors. Based on transfection assays gain-of-function studies frog mouse, transcription factor Gli1 proposed to be a major mediator signaling. To address whether this case we generated null allele expressing lacZ. Strikingly, not mouse development or viability. Of relevance, show that all...
ABSTRACT The correct patterning of vertebrate skeletal elements is controlled by inductive interactions. Two hedgehog proteins, Sonic and Indian hedgehog, have been implicated in development. During somite differentiation limb development, functions as an signal from the notochord, floor plate zone polarizing activity. Later skeletogenesis, a regulator chondrogenesis during endochondral ossification. Gli zinc finger proteins are putative transcription factors that respond to Hedgehog...
Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and publicly available genome-wide collection mouse knockouts would be significantly enabling for biomedical discovery. To date, published exist only about 10% genes. Furthermore, many these are limited utility because they have not been made or phenotyped standardized ways, freely to researchers. It is time harness new technologies efficiencies production mount high-throughput international effort...
ABSTRACT During mouse development, the homeobox-containing gene En-1 is specifically expressed across mid-hindbrain junction, ventral ectoderm of limb buds, and in regions hindbrain, spinal cord, somites somite-derived tissues. To address function during embryogenesis, we have generated mice homozygous for a targeted deletion homeobox. mutant died shortly after birth exhibited multiple developmental defects. In brains newborn mutants, most colliculi cerebellum were missing third fourth...
Gli2 and Gli3 are the primary transcription factors that mediate Sonic hedgehog (Shh) signals in mouse. mainly acts as a transcriptional repressor, because majority of full-length protein is proteolytically processed. mostly regarded activator, even though it also suggested to have weak repressing activity. What molecular basis for its possible dual function how activity regulated by Shh signaling largely unknown. Here we demonstrate unlike results seen with Cubitus Interruptus, fly homolog...
ABSTRACT Induction of the floor plate at ventral midline neural tube is one earliest events in establishment dorsoventral (d/v) polarity vertebrate central nervous system (CNS). The secreted molecule, Sonic hedgehog, has been shown to be both necessary and sufficient for this induction. In vertebrates, several downstream components signalling pathway have identified, including members Gli transcription factor family. study, we examined d/v patterning CNS Gli2 mouse mutants. We found that...
A strategy was devised for identifying regions of the mouse genome that are transcriptionally active in a temporally and spatially restricted manner during development. The approach is based on introduction into embryonic stem cells two types lacZ reporter constructs can be activated by flanking genomic sequences. Embryonic containing were used to produce chimaeric mice. Developmental regulation expression occurred at high frequency. Molecular cloning endogenous genes these potential...