A5020135419- Hearing, Cochlea, Tinnitus, Genetics
- Axon Guidance and Neuronal Signaling
- Developmental Biology and Gene Regulation
- Neurogenesis and neuroplasticity mechanisms
- Hearing Loss and Rehabilitation
- Hedgehog Signaling Pathway Studies
- Hippo pathway signaling and YAP/TAZ
- Neural dynamics and brain function
- Biochemical Analysis and Sensing Techniques
- Retinal Development and Disorders
- Neurobiology and Insect Physiology Research
- Congenital heart defects research
- Nerve injury and regeneration
- Wnt/β-catenin signaling in development and cancer
- Zebrafish Biomedical Research Applications
- Vestibular and auditory disorders
- Cellular transport and secretion
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Cellular Mechanics and Interactions
- Marine animal studies overview
- Receptor Mechanisms and Signaling
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
Harvard University
2016-2025
Harvard University Press
2007-2024
Stanford University
1996-2024
Brown University
2024
Thomas Jefferson University
2024
Palo Alto University
2024
Allen Institute for Brain Science
2024
Providence College
2024
Boston VA Research Institute
2023
Howard Hughes Medical Institute
1996-2001
The basal cell nevus syndrome (BCNS) is characterized by developmental abnormalities and the postnatal occurrence of cancers, especially carcinomas (BCCs), most common human cancer. Heritable mutations in BCNS patients a somatic mutation sporadic BCC were identified homolog Drosophila patched (ptc) gene. ptc gene encodes transmembrane protein that acts opposition to Hedgehog signaling protein, controlling fates, patterning, growth numerous tissues. PTC appears be crucial for proper embryonic...
The PATCHED (PTC) gene encodes a Sonic hedgehog (Shh) receptor and tumor suppressor protein that is defective in basal cell nevus syndrome (BCNS). Functions of PTC were investigated by inactivating the mouse gene. Mice homozygous for ptc mutation died during embryogenesis found to have open overgrown neural tubes. Two Shh target genes, itself Gli, derepressed ectoderm mesoderm but not endoderm. targets are, under normal conditions, transcribed ventrally aberrantly expressed dorsal lateral...
The signaling protein Hedgehog (Hh) controls cell fate and polarizes tissues in both flies vertebrates. In flies, Hh exerts its effects by opposing the function of a novel transmembrane protein, Patched, while also locally inducing patched (ptc) transcription. We have identified mouse homolog ptc which many is transcribed near cells making either Sonic or Indian hedgehog. addition, ectopic hedgehog expression central nervous system induces As transcription appears to be indicative signal...
The origin of new morphological characters is a long-standing problem in evolutionary biology. Novelties arise through changes development, but the nature these largely unknown. In butterflies, eyespots have evolved as pattern elements that develop from special organizers called foci. Formation foci associated with novel expression patterns Hedgehog signaling protein, its receptor Patched, transcription factor Cubitus interruptus, and engrailed target gene break conserved compartmental...
ABSTRACT Signalling by members of the Hedgehog family secreted proteins plays a central role in development vertebrate and invertebrate embryos. In Drosophila, transduction signal is intimately associated with activity protein kinase A product segment polarity gene patched. We have cloned homologue patched from zebrafish Danio rerio analysed spatiotemporal regulation its transcription during embryonic both wild-type mutant animals. find striking correlation between accumulation patched1...
ABSTRACT Hedgehog genes have been implicated in inductive signaling during development a variety of organisms. A key element the hedgehog system is encoded by gene patched. In Drosophila regulates expression antagonizing action addition, patched itself transcriptional target signaling. We isolated chicken homolog and find it to be strongly expressed adjacent all tissues where members family are expressed. As Drosophila, ectopic Sonic leads induction Patched. Based on this regulatory...
Cochlear ganglion neurons communicate sound information from cochlear hair cells to auditory brainstem through precisely wired circuits. Understanding circuit assembly is a significant challenge because of the small size otic vesicle and difficulties labeling imaging embryonic neurons. We used genetic fate mapping in mouse visualize morphologies individual throughout development, their origin Neurogenin1 -positive neurogenic domain formation connections with targets cochlea nucleus. found...
Temporal and spatial coordination of multiple cell fate decisions is essential for proper organogenesis. Here, we define gene interactions that transform the neurogenic epithelium developing inner ear into specialized mechanosensory receptors. By Cre-loxP mapping, show vestibular sensory hair cells derive from a previously region ear. The related bHLH genes Ngn1 (Neurog1) Math1 (Atoh1) are required, respectively, neural epithelial development in this system. Our analysis mouse mutants...
Vestibular hair cells have a distinct planar cell polarity (PCP) manifest in the morphology of their stereocilia bundles and asymmetric localization kinocilia. In utricle saccule are arranged an orderly array about abrupt line reversal that separates fields with opposite polarity. We report putative PCP protein Prickle-like 2 (Pk2) is distributed crescents on medial sides vestibular epithelial before morphological polarization cells. Despite presence reversal, crescent position not altered...
The sense of hearing depends on the faithful transmission sound information from ear to brain by spiral ganglion (SG) neurons. However, how SG neurons develop connections and properties that underlie auditory processing is largely unknown. We catalogued gene expression in mouse embryonic day 12, when first extend projections, up until postnatal 15, after onset hearing. For comparison, we also analyzed closely related vestibular (VG). Gene ontology analysis confirmed enriched genes associated...
Experiments utilizing the Looptail mutant mouse, which harbors a missense mutation in vangl2 gene, have been essential for studies of planar polarity and linking function core cell proteins to other developmental signals. Originally described as having dominant phenotypic traits, molecular interactions underlying phenotype are unclear because Vangl2 protein levels significantly reduced or absent from tissues. Here we introduce knockout mouse directly compare severity phenotypes by...
β-Cell proliferation and expansion during pregnancy are crucial for maintaining euglycemia in response to increased metabolic demands placed on the mother. Prolactin placental lactogen signal through prolactin receptor (PRLR) contribute adaptive β-cell responses pregnancy; however, vivo requirement PRLR signaling specifically maternal adaptations remains unknown. We generated a floxed allele of Prlr, allowing conditional loss β-cells. In this study, we show that β-cells results gestational...
Abstract The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the to cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled total 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into companion atlas whole mouse 1 . This taxonomy reveals three-component organization SPNs: (1) molecularly homogeneous excitatory cortex, red...
Brainstem olivocochlear neurons (OCNs) modulate the earliest stages of auditory processing through feedback projections to cochlea and have been shown influence hearing protect ear from sound-induced damage. Here, we used single-nucleus sequencing, anatomical reconstructions, electrophysiology characterize murine OCNs during postnatal development, in mature animals, after sound exposure. We identified markers for known medial (MOC) lateral (LOC) OCN subtypes, show that they express distinct...
Vision is initiated by the reception of light photoreceptors and subsequent processing via downstream retinal neurons. Proper circuit organization depends on multifunctional tissue polarity protein FAT3, which required for amacrine cell connectivity lamination. Here, we investigated function Fat3 mutant mice found decreases in both electroretinography perceptual responses to high-frequency flashes. These defects did not correlate with abnormal wiring, pointing instead a role bipolar subtypes...
Leucine-rich repeat-containing, G protein-coupled receptors (LGRs) belong to the largest mammalian superfamily of proteins with seven-transmembrane domains. LGRs can be divided into three subgroups based on their unique domain arrangement. Although two have been found for glycoprotein hormones and relaxin-related ligands, respectively, third LGR subgroup, consisting LGR4-6, are orphan unknown physiological roles. To elucidate functions this subgroup LGRs, LGR4 null mice were generated using...
The atypical cadherin fat (ft) was originally discovered as a tumor suppressor in Drosophila and later shown to regulate form of tissue patterning known planar polarity. In mammals, four ft homologs have been identified (Fat1-4). Recently, we demonstrated that Fat4 plays role vertebrate has the highest homology ft, whereas other Fat family members are homologous second ft-like gene, ft2. Genetic studies flies mice imply significant functional differences between two groups cadherins. Here,...