A5077255106- Developmental Biology and Gene Regulation
- Pluripotent Stem Cells Research
- Neurogenesis and neuroplasticity mechanisms
- CRISPR and Genetic Engineering
- Congenital heart defects research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- 3D Printing in Biomedical Research
- Zebrafish Biomedical Research Applications
- Epigenetics and DNA Methylation
- Plant Molecular Biology Research
- Axon Guidance and Neuronal Signaling
- Retinal Development and Disorders
- Sperm and Testicular Function
- Genomics and Chromatin Dynamics
- Animal Genetics and Reproduction
- Wnt/β-catenin signaling in development and cancer
- Single-cell and spatial transcriptomics
- Genetics and Neurodevelopmental Disorders
- Hearing, Cochlea, Tinnitus, Genetics
- Genetics, Aging, and Longevity in Model Organisms
- Hedgehog Signaling Pathway Studies
- Hippo pathway signaling and YAP/TAZ
- Drug Transport and Resistance Mechanisms
- RNA Research and Splicing
- Neurobiology and Insect Physiology Research
University of Lisbon
2008-2024
Instituto de Medicina Molecular João Lobo Antunes
2002-2022
Champalimaud Foundation
2010-2015
Hospital de Dona Estefânia
2015
Instituto Gulbenkian de Ciência
2002-2011
National Legal Medicine Institute
2010
Hospital de Egas Moniz
1998-2009
Mount Sinai Hospital
2004
University of Toronto
2004
Lunenfeld-Tanenbaum Research Institute
2004
Involvement of the Notch signaling pathway in vascular development has been demonstrated by both gain- and loss-of-function mutations humans, mice, zebrafish. In zebrafish, is required for arterial identity suppressing venous fate developing artery cells. Notch4 receptor Delta-like 4 (Dll4) ligand are specifically expressed endothelial cells, suggesting a similar role. Here we show that Dll4 alone dosage-sensitive manner normal patterning development. This implicates as specific mammalian...
ABSTRACT Mouse delta-like 3 (Dll3), a novel vertebrate homologue of the Drosophila gene Delta was isolated by subtracted library screen. In Drosphila, Delta/Notch signalling pathway functions in many situations both embryonic and adult life where cell fate specification occurs. addition, patterning role has been described establishment dorsoventral compartment boundary wing imaginal disc. Dll3 is most divergent identified to date. We confirm that can inhibit primary neurogenesis when...
Notch signaling is known to differentially affect the development of lymphoid B and T cell lineages, but it remains unclear whether such effects are specifically dependent on distinct ligands. Using a coculture assay we observed that ligand Delta-1 completely inhibits differentiation human hematopoietic progenitors into lineage while promoting emergence cells with phenotype cell/natural killer (NK) precursors. In contrast, Jagged-1 did not disturb either or cell/NK development. Furthermore,...
ABSTRACT Somitic segmentation provides the framework on which segmental pattern of vertebrae, some muscles and peripheral nervous system is established. Recent evidence indicates that a molecular oscillator, ‘segmentation clock’, operates in presomitic mesoderm (PSM) to direct periodic expression c-hairy1 lunatic fringe (l-fng). Here, we report identification characterisation second avian hairy-related gene, c-hairy2, also cycles PSM whose sequence closely related mammalian HES1 downstream...
The sensory patches in the vertebrate inner ear are similar function to mechanosensory bristles of a fly, and consist set cell types. If they truly homologous structures, should also develop by mechanisms. We examine genesis neurons, hair cells supporting that form chick. These all arise from otic epithelium, produced normally even epithelium cultured isolation, confirming their production is governed mechanisms intrinsic epithelium. First, neuronal sublineage becomes separate epithelial:...
U Strähle, P Blader, D Henrique, and W Ingham Department of Zoology, Molecular Embryology Laboratory Developmental Genetics Laboratory, University Oxford, UK.
In Drosophila, cells are thought to be singled out for a neural fate through competitive mechanism based on lateral inhibition mediated by Delta-Notch signalling. tetrapod vertebrates, nascent neurons express the Delta1 gene and thereby deliver their neighbours, but it is not clear how these within neurectoderm in first place. We have found four Delta homologues zebrafish--twice as many reported any vertebrate. Three of these--deltaA, deltaB deltaD--are involved primary neurogenesis, while...
The in vitro generation of neurons from embryonic stem (ES) cells is a promising approach to produce suitable for neural tissue repair and cell-based replacement therapies the nervous system. Available methods promote ES cell differentiation towards lineages attempt replicate, different ways, multistep process development. However, achieve this aim an efficient reproducible way, better knowledge cellular molecular events that are involved process, initial specification neuroepithelial...
Heterogeneous expression of the transcription factor NANOG has been linked to existence various functional states in pluripotent stem cells. This heterogeneity seems arise from fluctuations Nanog individual cells, but a thorough characterization these and their impact on state is still lacking. Here, we have used novel fluorescent reporter investigate temporal dynamics mouse embryonic cells (mESCs), dissect lineage potential mESCs at different states. Our results show that stochastic are...
ABSTRACT Mechanosensory hair cells (HCs) are the primary receptors of our senses hearing and balance. Elucidation transcriptional networks regulating HC fate determination differentiation is crucial not only to understand inner ear development but also improve cell replacement therapies for disorders. Here, we show that combined expression transcription factors Gfi1, Pou4f3 Atoh1 can induce direct programming towards fate, both during in vitro mouse embryonic stem following ectopic chick...
ABSTRACT Serrate-like genes encode transmembrane ligands to Notch receptors and control cell fate decisions during development. In this report, we analyse the regulation of mouse Serrate-1 gene embryogenesis. The is expressed from embryonic day 7.5 (E7.5) expression often observed at sites epithelial-mesenchymal interactions, including developing tooth, where first (E11.5) in all cells dental epithelium, but not mesenchyme. A transient upregulation mesenchyme (E12.5-15.5) correlated with...
ABSTRACT During Drosophila myogenesis, Notch signalling acts at multiple steps of the muscle differentiation process. In vertebrates, activation has been shown to block MyoD and in vitro, suggesting that this pathway may act maintain cells an undifferentiated proliferative state. paper, we address role vivo during chick myogenesis. We first demonstrate Notch1 receptor is expressed postmitotic myotome ligands Delta1 Serrate2 are detected subsets differentiating myogenic thus position signal...
Abstract Embryonic stem (ES) cells have been shown to differentiate in vitro into a wide variety of cell types having significant potential for tissue regeneration. Therefore, the operational conditions ex vivo expansion and differentiation should be optimized large‐scale cultures. The mouse ES has evaluated static culture. However, this system, culture parameters are difficult monitor scaling‐up becomes time consuming. use stirred bioreactors facilitates under controlled but,...
ABSTRACT Chick embryonic feather buds arise in a distinct spatial and temporal pattern. Although many genes are implicated the growth differentiation of buds, little is known about how discrete pattern array formed which gene products may be involved. Possible candidates include Notch its ligands, Delta Serrate, as they play role numerous cell fate decisions organisms. Here we show that Notch-1 Notch-2 mRNAs expressed skin localized prior to bud initiation. In early stages development,...