- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neuropharmacology Research
- Developmental Biology and Gene Regulation
- Epigenetics and DNA Methylation
- Axon Guidance and Neuronal Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- MicroRNA in disease regulation
- Congenital heart defects research
- Single-cell and spatial transcriptomics
- Pluripotent Stem Cells Research
- Microtubule and mitosis dynamics
- Genetics and Neurodevelopmental Disorders
- Nerve injury and regeneration
- Congenital gastrointestinal and neural anomalies
- Memory and Neural Mechanisms
- Renal and related cancers
- Glioma Diagnosis and Treatment
- RNA Research and Splicing
- Hedgehog Signaling Pathway Studies
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Receptor Mechanisms and Signaling
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Circadian rhythm and melatonin
- PI3K/AKT/mTOR signaling in cancer
University College London
2015-2024
Wolfson Foundation
2006-2024
University College Lahore
2017
UCL Australia
2011
Max Planck Institute for Molecular Biomedicine
2010
University of Colorado Boulder
2008
University of Namur
2008
Cincinnati Children's Hospital Medical Center
2008
Albert Einstein College of Medicine
2008
UCLouvain
2008
Astrocytes, the most abundant cell population in central nervous system (CNS), are essential for normal neurological function. We show that astrocytes allocated to spatial domains mouse spinal cord and brain accordance with their embryonic sites of origin ventricular zone. These remain stable throughout life without evidence secondary tangential migration, even after acute CNS injury. Domain-specific depletion ventral resulted abnormal motor neuron synaptogenesis, which was not rescued by...
Cortical pyramidal cells are generated from pallial neuroepithelial precursors, whereas GABAergic interneurons originate in subpallial germinal zones and migrate tangentially to reach the cortex. Using Cre–lox technology transgenic mice a series of molecular markers that subdivide neuroepithelium into small domains, we fate-map precursor pools identify each domain. expressing calbindin, parvalbumin, somatostatin exclusively Lhx6 (Lim homeobox 6)-expressing precursors medial ganglionic...
The enteric nervous system (ENS) in mammals forms from neural crest cells during embryogenesis and early postnatal life. Nevertheless, multipotent progenitors of the ENS can be identified adult intestine using clonal cultures vivo transplantation assays. identity these neurogenic precursors gut their relationship to embryonic are currently unknown. Using genetic fate mapping, we here demonstrate that mouse marked by SRY box-containing gene 10 (Sox10) generate neuronal glial lineages ganglia....
In the gray matter of brain, astrocytes have been suggested to export lactate (derived from glucose or glycogen) neurons power their mitochondria. white matter, can support axon function in conditions energy deprivation, but it is not known whether acts by preserving levels axons oligodendrocytes, myelinating processes which are damaged rapidly low conditions. Studies cultured cells suggest that oligodendrocytes cell type brain consumes at highest rate, part produce membrane lipids...
We determined the embryonic origins of adult forebrain subventricular zone (SVZ) stem cells by Cre-lox fate mapping in transgenic mice. found that all parts telencephalic neuroepithelium, including medial ganglionic eminence and lateral (LGE) cerebral cortex, contribute multipotent, self-renewing to SVZ. Descendants LGE cortex settle ventral dorsal aspects dorsolateral SVZ, respectively. Both populations new (5-bromo-2′-deoxyuridine-labeled) tyrosine hydroxylase- calretinin-positive...
Extracellular ATP controls various signaling systems including propagation of intercellular Ca 2+ signals (ICS). Connexin hemichannels, P2x7 receptors (P2x7Rs), pannexin channels, anion vesicles, and transporters are putative conduits for release, but their involvement in ICS remains controversial. We investigated cochlear organotypic cultures, which acts as an IP 3 -generating agonist evokes responses that have been linked to noise-induced hearing loss development hair cell-afferent...
Understanding any brain circuit will require a categorization of its constituent neurons. In hippocampal area CA1, at least 23 classes GABAergic neuron have been proposed to date. However, this list may be incomplete; additionally, it is unclear whether discrete are sufficient describe the diversity cortical inhibitory neurons or continuous modes variability also required. We studied transcriptomes 3,663 CA1 cells, revealing 10 major groups that divided into 49 fine-scale clusters. All...
In the caudal neural tube, oligodendrocyte progenitors (OLPs) originate in ventral neuroepithelium under influence of Sonic hedgehog (SHH), then migrate throughout spinal cord and brainstem before differentiating into myelin-forming cells. We present evidence that oligodendrogenesis anterior tube follows a similar pattern. show OLPs embryonic mouse forebrain express platelet-derived growth factor alpha-receptors (PDGFRA), as they do more regions. They first appear within region hypothalamic...
Fat cells (adipocytes) develop from adipocyte precursor (preadipocytes) that themselves derive mesenchymal progenitors. Although the events controlling preadipocyte differentiation into mature adipocytes have been largely explored, mechanisms direct progenitors down pathway remain unknown. Similarly, although are generally thought to mesoderm, key information is lacking regarding origin and development of adipose tissue during embryogenesis. The aim this study was gain insight ontogeny fat...
GABA-containing (GABAergic) interneurons play an important role in the function of cerebral cortex. Through mostly inhibitory mechanisms, control hyperexcitability and synchronize shape spatiotemporal dynamics cortical activity underlying various brain functions. Studies over past 10 years have demonstrated that, most mammals, originate during development from subcortical telencephalon—the subpallium—and reach cortex through tangential migration. Until now, been to derive exclusively two...
Many oligodendrocytes in the spinal cord are derived from a region of ventral ventricular zone (VZ) that also gives rise to motoneurons. Cell fate specification this depends on sonic hedgehog (Shh) notochord and floor plate. There have been suggestions an additional source(s) dorsal cord. We revisited idea by Cre-lox fate-mapping transgenic mice. found subpopulation is generated Dbx1-expressing domain VZ, spanning dorsoventral midline. Dbx-derived comprise less than 5% total; they formed...
In the developing spinal cord, most oligodendrocyte precursors (OLPs) arise from ventral ventricular zone (VZ) under influence of Sonic Hedgehog, but a minority are generated dorsal VZ in Hedgehog-independent manner. forebrain too, OLPs both and VZ. It is not known whether dorsally ventrally derived (OL) lineage cells have different properties. We dual reporter mouse line to color code (vOLPs dOLPs) their differentiated progeny (vOLs dOLs) for functional studies. found that ∼80% OL postnatal...
Development of axonal tracts requires interactions between growth cones and the environment. Tracts such as anterior commissure internal capsule are defective in mice with null mutation Celsr3. We generated a conditional Celsr3 allele, allowing regional inactivation. Inactivation telencephalon, ventral forebrain, or cortex demonstrated essential roles for neurons that project axons to subcerebral targets, well cells guide through capsule. When was inactivated cortex, projections failed grow,...
Neural stem cells (NSCs) are slowly dividing astrocytes that intimately associated with capillary endothelial in the subventricular zone (SVZ) of brain. Functionally, members vascular growth factor (VEGF) family can stimulate neurogenesis as well angiogenesis, but it has been unclear whether they act directly via VEGF receptors (VEGFRs) expressed by neural cells, or indirectly release factors from angiogenic capillaries. Here, we show VEGFR-3, a receptor required for lymphangiogenesis, is...
Transcriptional codes initiated during brain development are ultimately realized in adulthood as distinct cell types performing specialized roles behavior. Focusing on the mouse external globus pallidus (GPe), we demonstrate that potential contributions of two GABAergic GPe to voluntary action fated from early life be distinct. Prototypic neurons derive medial ganglionic eminence embryonic subpallium and express transcription factor Nkx2-1. These fire at high rates alert rest, encode...
Wnt/β-catenin signaling controls multiple steps of neural crest development, ranging from induction, lineage decisions, to differentiation. In mice, conditional β-catenin inactivation in premigratory cells abolishes both sensory neuron and melanocyte formation. Intriguingly, the generation melanocytes is also prevented by activation crest, which promotes neurogenesis at expense other derivatives. This raises question how regulates formation distinct lineages crest. Using various Cre lines...