- Developmental Biology and Gene Regulation
- Congenital heart defects research
- Hedgehog Signaling Pathway Studies
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Neurogenesis and neuroplasticity mechanisms
- Axon Guidance and Neuronal Signaling
- MicroRNA in disease regulation
- Genomics and Chromatin Dynamics
- Congenital gastrointestinal and neural anomalies
- Wnt/β-catenin signaling in development and cancer
- Cancer-related molecular mechanisms research
- Pluripotent Stem Cells Research
- Cell Adhesion Molecules Research
- Epigenetics and DNA Methylation
- Animal Genetics and Reproduction
- Cleft Lip and Palate Research
- RNA Research and Splicing
- Craniofacial Disorders and Treatments
- Congenital Ear and Nasal Anomalies
- Hippo pathway signaling and YAP/TAZ
- Proteoglycans and glycosaminoglycans research
- Zebrafish Biomedical Research Applications
- Ichthyology and Marine Biology
- Single-cell and spatial transcriptomics
- Congenital Anomalies and Fetal Surgery
California Institute of Technology
2016-2025
University of Edinburgh
2022
University of Zurich
2020
Johns Hopkins University
1980-2020
Saint Mary's College
2020
Trinity Health Oakland Hospital
2020
Max Planck Institute for Heart and Lung Research
2019
Stowers Institute for Medical Research
2017
University of California, Los Angeles
2003-2014
Imaging Center
2010
Pediatric brain tumors are significant causes of morbidity and mortality. It has been hypothesized that they derive from self-renewing multipotent neural stem cells. Here, we tested whether different pediatric tumors, including medulloblastomas gliomas, contain cells with properties similar to We find tumor-derived progenitors form neurospheres can be passaged at clonal density able self-renew. Under conditions promoting differentiation, individual multipotent, giving rise both neurons glia,...
Lancelets (‘amphioxus’) are the modern survivors of an ancient chordate lineage, with a fossil record dating back to Cambrian period. Here we describe structure and gene content highly polymorphic ∼520-megabase genome Florida lancelet Branchiostoma floridae, analyse it in context evolution. Whole-genome comparisons illuminate murky relationships among three groups (tunicates, lancelets vertebrates), allow not only reconstruction complement last common ancestor but also partial its genomic...
Jeramiah Smith, Weiming Li and colleagues report the whole-genome sequence of sea lamprey, Petromyzon marinus, representing a vertebrate lineage diverged from humans ~500 million years ago. Their analyses define key evolutionary events in lineages provide evidence for two duplication occurring before divergence ancestral lamprey jawed (gnathostome) lineages. Lampreys are representatives an ancient that our own ∼500 By virtue this deeply shared ancestry, (P. marinus) genome is uniquely poised...
Neural crest cells, which generate peripheral nervous system and facial skeleton, arise at the neural plate/ectodermal border via an inductive interaction between these tissues. Wnts bone morphogenetic proteins (BMPs) play roles in induction amphibians zebrafish. Here, we show that, avians, Wnt6 is localized ectoderm vivo inhibition of Wnt signaling perturbs formation. Furthermore, induce from naı̈ve plates vitro a defined medium without added factors, whereas BMPs require additives. Our...
Cephalochordates, urochordates, and vertebrates evolved from a common ancestor over 520 million years ago. To improve our understanding of chordate evolution the origin vertebrates, we intensively searched for particular genes, gene families, conserved noncoding elements in sequenced genome cephalochordate Branchiostoma floridae, commonly called amphioxus or lancelets. Special attention was given to homeobox opsin genes involved neural crest development, nuclear receptor encoding components...
ABSTRACT We have investigated the molecular interactions underlying neural crest formation in Xenopus. Using chordin overexpression to antagonize endogenous BMP signaling whole embryos and explants, we demonstrate that such inhibition alone is insufficient account for induction vivo. find, however, chordin-induced plate tissue can be induced adopt fates by members of FGF Wnt families, growth factors previously been shown posteriorize tissue. Overexpression a dominant negative XWnt-8 inhibits...
The spatial and temporal aspects of cranial neural crest cell migration in the mouse are poorly understood because technical limitations. No reliable markers available vital staining embryos culture has had limited success they develop normally for only 24 hours. Here, we circumvent these problems by combining dye labelling with exo utero embryological techniques. To define better nature embryo, premigratory cells were labelled injecting DiI into amniotic cavity on embryonic day 8. Embryos,...
Neural crest cells are embryonic progenitors that generate numerous cell types in vertebrates. With single-cell analysis, we show mouse trunk neural become biased toward neuronal lineages when they delaminate from the tube, whereas cranial acquire ectomesenchyme potential dependent on activation of transcription factor Twist1. The choices make to sensory, glial, autonomic, or mesenchymal can be formalized as a series sequential binary decisions. Each branch decision tree involves initial...
ABSTRACT We have investigated the lineage and tissue interactions that result in avian neural crest cell formation from ectoderm. Presumptive plate was grafted adjacent to non-neural ectoderm whole embryo culture examine role of ontogeny crest. Our results show juxtaposition nonneural presumptive induces cells. Quail/chick recombinations demonstrate both prospective epidermis can contribute When similar plate/epidermal confrontations are performed look at derivatives, with either early...
ABSTRACT To permit a more detailed analysis of neural crest cell migratory pathways in the chick embryo, cells were labelled with nondeleterious membrane intercalating vital dye, Dil. All tube endfeet contact lumen, including premigratory cells, by pressure injecting solution Dil into lumen tube. When assayed one to three days later, migrating motor axons, and ventral root only types external During phase, distinctly found along: (1) dorsolateral pathway, under epidermis, as well adjacent...
The possible role of a 140-kD cell surface complex in neural crest adhesion and migration was examined using monoclonal antibody JG22, first described by Greve Gottlieb (1982, J. Cell. Biochem. 18:221-229). addition JG22 to cells vitro caused rapid change morphology plated on either fibronectin or laminin substrates. became round phase bright, often detaching from the dish forming aggregates rounded cells. Other tissues such as somites, notochords, tubes were unaffected even though antigen...
The Notch signaling pathway comprises multiple ligands that are used in distinct biological contexts. In principle, different could activate target programs signal-receiving cells, but it is unclear how such ligand discrimination occur. Here, we show cells use dynamics to discriminate by the Dll1 and Dll4 through Notch1 receptor. Quantitative single-cell imaging revealed activates discrete, frequency-modulated pulses specifically upregulate gene Hes1. By contrast, a sustained,...