A5081946465- Developmental Biology and Gene Regulation
- Axon Guidance and Neuronal Signaling
- Congenital heart defects research
- Neurogenesis and neuroplasticity mechanisms
- Genomics and Chromatin Dynamics
- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Photoreceptor and optogenetics research
- RNA Research and Splicing
- dental development and anomalies
- Retinal Development and Disorders
- Zebrafish Biomedical Research Applications
- Craniofacial Disorders and Treatments
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Cancer-related molecular mechanisms research
- Neuroscience of respiration and sleep
- Hearing, Cochlea, Tinnitus, Genetics
- Retinoids in leukemia and cellular processes
- Animal Genetics and Reproduction
- Wnt/β-catenin signaling in development and cancer
- Vestibular and auditory disorders
Friedrich Miescher Institute
2015-2025
University of Basel
2015-2025
Novartis (Switzerland)
2011-2017
Novartis Institutes for BioMedical Research
2017
Ehime University
2012
Centre National de la Recherche Scientifique
1998-2009
Inserm
1999-2009
Institut de génétique et de biologie moléculaire et cellulaire
2003-2009
University of Namur
2008
Institut de Biologie Moléculaire et Cellulaire
1998-2007
ABSTRACT Retinoids are essential for normal development and both deficiency excess of retinoic acid (RA) teratogenic. Retinoic response elements (RAREs) have been identified in Hox gene promoters suggesting that endogenous retinoids may be involved the direct control patterning functions. In order to test this hypothesis, we mutated Hoxa-1 3′ RARE using Cre-loxP targeting strategy, studied its functional role during mouse development. We find enhancer plays an important early establishment...
The analysis of Hoxa1 and Hoxb1 null mutants suggested that these genes are involved in distinct aspects hindbrain segmentation specification. Here we investigate the possible functional synergy two genes. generation Hoxa1(3'RARE)/Hoxb1(3'RARE) compound resulted mild facial motor nerve defects reminiscent those present mutants. Strong genetic interactions between were uncovered by introducing Hoxb1(3'RARE) mutations into background. Hoxa1(null)/Hoxb1(3'RARE) Hoxa1(null)/Hoxb1(null )double...
ABSTRACT In the developing vertebrate hindbrain Hoxa1 and Hoxb1 play important roles in patterning segmental units (rhombomeres). this study, genetic analysis of double mutants demonstrates that both participate establishment maintenance expression rhombomere 4 through auto- para-regulatory interactions. The generation a targeted mutation 3′ retinoic acid response element (RARE) shows it is required for establishing early high levels neural ectoderm. Double mutant with Hoxb13′RARE allele...
Neural progenitor cells often produce distinct types of neurons in a specific order, but the determinants that control sequential generation neuronal subclasses vertebrate CNS remain poorly defined. We examined visceral motor and serotonergic from common pool neural progenitors located ventral hindbrain. found temporal specification these varies along anterior-posterior axis hindbrain, timing their critically depends on integrated activities Nkx- Hox-class homeodomain proteins. A primary...
ABSTRACT Segmentation plays an important role in neuronal diversification and organisation the developing hindbrain. For instance, cranial nerve branchiomotor nuclei are organised segmentally within basal plates of successive pairs rhombomeres. To reach their targets, motor axons follow highly stereotyped pathways exiting hindbrain only via specific exit points even-numbered Hox genes good candidates for controlling this pathfinding, since they expressed involved rhom-bomeric patterning....
ABSTRACT Hox genes are required to pattern neural crest (NC) derived craniofacial and visceral skeletal structures. However, the temporal requirement of patterning activity is not known. Here, we use an inducible system establish Hoxa2 at distinct NC migratory stages in Xenopus embryos. We uncover stage-specific effects gain-of-function suggesting a multistep process for hindbrain NC. Most interestingly, show that induction postmigratory results mirror image homeotic transformation subset...
Abstract The cerebral cortex is organized into specialized sensory areas, whose initial territory determined by intracortical molecular determinants. Yet, cortical area size appears to be fine tuned during development respond functional adaptations. Here we demonstrate the existence of a prenatal sub-cortical mechanism that regulates areas in mice. This mediated spontaneous thalamic calcium waves propagate among sensory-modality nuclei up and provide means communication systems. Wave pattern...
The cranial neural crest cells are multipotent that provide head skeletogenic mesenchyme and crucial for craniofacial patterning. We analyzed the chromatin landscapes of mouse subpopulations in vivo. Early postmigratory contributing to distinct structures displayed similar accessibility patterns yet differed transcriptionally. Accessible promoters enhancers differentially silenced genes carried H3K27me3/H3K4me2 bivalent marks embedded large enhancer zeste homolog 2-dependent Polycomb...
We investigated the role of histone methyltransferase Ezh2 in tangential migration mouse precerebellar pontine nuclei, main relay between neocortex and cerebellum. By counteracting sonic hedgehog pathway, represses Netrin1 dorsal hindbrain, which allows normal neuron migration. In mutants, ectopic derepression results abnormal supernumerary nuclei integrating brain circuitry. Moreover, intrinsic topographic organization according to rostrocaudal progenitor origin is maintained throughout...
Abstract Summary Proteins binding to specific nucleotide sequences, such as transcription factors, play key roles in the regulation of gene expression. Their can be indirectly observed via associated changes transcription, chromatin accessibility, DNA methylation and histone modifications. Identifying candidate factors that are responsible for these experimental is critical understand underlying biological processes. Here, we present monaLisa, an R/Bioconductor package implements approaches...
Homozygous mice mutated by homologous recombination for the AbdB-related Hoxa-10 gene are viable but display homeotic transformations of vertebrae and lumbar spinal nerves. Mutant males exhibit unilateral or bilateral criptorchidism due to developmental abnormalities gubernaculum, resulting in abnormal spermatogenesis sterility. These results reveal an important role patterning posterior body regions suggest that Hox genes involved specifying regional identity both segmented nonovertly...
ABSTRACT The Abdominal B-related Hoxa-10 gene displays similar expression patterns in the differentiating forelimbs and hindlimbs of mouse, with preferential around humeral femoral cartilages more diffuse distal regions. We found that a targeted disruption has almost no effect forelimbs, while it affects proximal hindlimb skeleton. alterations were located along dorsolateral side femur (labium laterale), an enlargement shift third trochanter, misshapen lateral knee sesamoid, supernumerary...
The pontine neurons (PN) represent a major source of mossy fiber projections to the cerebellum. During mouse hindbrain development, PN migrate tangentially and sequentially along both anteroposterior (AP) dorsoventral (DV) axes. Unlike DV migration, which is controlled by Netrin-1/Dcc attractive pathway, little known about molecular mechanisms guiding migration AP axis. Here, we show that Hoxa2 Hoxb2 are required intrinsically extrinsically maintain normal subsets PN, preventing their...
Little is known about the spatiotemporal requirement of Hox gene patterning activity in vertebrates. In Hoxa2 mouse mutants, hyoid skeleton replaced by a duplicated set mandibular and middle ear structures. Here, we show that selectively required cranial neural crest cells (NCCs). Moreover, used Cre-ERT2 recombinase system to induce temporally controlled deletion mouse. inactivation after NCC migration into branchial arches resulted homeotic transformation arch skeletal derivatives,...
In the mouse trigeminal pathway, sensory inputs from distinct facial structures, such as whiskers or lower jaw and lip, are topographically mapped onto somatosensory cortex through relay stations in thalamus hindbrain. developing hindbrain, mechanisms generating maps remain elusive. We found that principal nucleus, whisker-related map is contributed by rhombomere 3–derived neurons, whereas 2–derived progeny supply lip representation. Moreover, early Hoxa2 expression neuroepithelium prevents...