A5020448034- Developmental Biology and Gene Regulation
- Zebrafish Biomedical Research Applications
- Congenital heart defects research
- Hedgehog Signaling Pathway Studies
- Neurogenesis and neuroplasticity mechanisms
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Plant Molecular Biology Research
- Cancer-related molecular mechanisms research
- Congenital limb and hand anomalies
- Chromosomal and Genetic Variations
- Marine Biology and Environmental Chemistry
- Marine Ecology and Invasive Species
- Animal Genetics and Reproduction
- Protist diversity and phylogeny
- Polymer-Based Agricultural Enhancements
- Genetics and Neurodevelopmental Disorders
- Genetics, Bioinformatics, and Biomedical Research
- Material Dynamics and Properties
- Medical Research and Treatments
- Genetic and phenotypic traits in livestock
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Syracuse University
2011-2024
ORCID
2019
University of Cambridge
2005-2011
Max Planck Institute for Developmental Biology
2004
Institute of Molecular and Cell Biology
2004
University of Sheffield
1999-2004
University of Oregon
2001-2004
The Honourable Society of Lincoln's Inn
1996-1999
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...
Sonic hedgehog (Shh) signaling patterns many vertebrate tissues. shh mutations dramatically affect mouse ventral forebrain and floor plate but produce minor defects in zebrafish. Zebrafish have two mammalian Shh orthologs, sonic tiggy-winkle hedgehog, another gene, echidna that could overlapping functions. To examine the role of Hedgehog zebrafish, we characterized slow muscle omitted (smu) mutants. We show smu encodes a zebrafish ortholog Smoothened transduces signals. smoothened is...
ABSTRACT It has been proposed that digit identity in chick limb bud is specified a dose-dependent fashion by long-range morphogen, produced the polarising region. One candidate Sonic hedgehog (Shh) protein, but it not clear whether Shh acts long or short range via Bmps. Here we dissect relationship between and Bmp signalling. We show necessary only for initiating bmp2 expression also sustaining its during period when additional digits are being specified. can reproduce much of effect this...
Signaling by lipid-modified secreted glycoproteins of the Hedgehog family play fundamental roles during pattern formation in animal development and humans; dysfunction pathway components is frequently associated with a variety congenital abnormalities cancer. Transcriptional regulation target genes mediated members Gli zinc-finger transcription factors. The relative nuclear concentrations activator (Gli act ) repressor rep forms, together their nucleocytoplasmic trafficking, appear to be...
Sonic hedgehog (Shh) is crucial for motoneuron development in chick and mouse. However, zebrafish embryos homozygous a deletion of the shh locus have normal numbers motoneurons, raising possibility that motoneurons may be specified differently. Unlike other vertebrates, express three hh genes embryonic midline: shh, echidna (ehh) tiggywinkle (twhh). Therefore, it possible Twhh Ehh are sufficient formation absence Shh. To test this hypothesis we eliminated, or severely reduced, all Hh signals...
ABSTRACT talpid 3 is an embryonic-lethal chicken mutation in a molecularly un-characterised autosomal gene. The recessive, pleiotropic phenotype includes polydactylous limbs with morphologically similar digits. Previous analysis established that hox-D and bmp genes, are normally expressed posteriorly the limb bud response to localised, posterior source of Sonic Hedgehog (Shh) symmetrically across entire anteroposterior axis talpid3 buds. In contrast, Shh expression itself unaffected. Here we...
V1 interneurons are inhibitory neurons that play an essential role in vertebrate locomotion. The molecular mechanisms underlying their genesis remain, however, largely undefined. Here, we show the transcription factor Prdm12 is selectively expressed p1 progenitors of hindbrain and spinal cord frog embryo, a similar restricted expression profile observed nerve other vertebrates as well cephalochordate amphioxus. Using frog, chick mice, analyzed regulation found its caudal neural tube...
Vertebrate locomotor circuitry contains distinct classes of ventral spinal cord neurons which each have particular functional properties. While we know some the genes expressed by these cell types, do not yet how several are specified. Here, investigate functions Tal1, Gata2a, and Gata3 transcription factors in development two populations with important roles circuitry: V2b cerebrospinal fluid-contacting Kolmer-Agduhr (KA) (also called CSF-cNs). Our data provide first demonstration, any...
For neurons to function correctly in neuronal circuitry they must utilize appropriate neurotransmitters. However, even though neurotransmitter specificity is one of the most important and defining properties a neuron we still do not fully understand how fates are specified during development. Most determined by transcription factors that express as start differentiate. While know few specify particular neurons, there many spinal for which specifying this critical phenotype unknown....
The spinal cord contains several distinct classes of neurons but it is still unclear how many the functional characteristics these cells are specified. One most crucial a neuron its neurotransmitter fate. In this paper, we show that in zebrafish glycinergic and GABAergic interneurons express Pax2a, Pax2b Pax8 transcription factors redundantly required for fates cells. We also demonstrate function Pax2/8 very specific: embryos which simultaneously knocked-down, lose their and/or...
Abstract The transcription factor Evx1 is expressed in the joints between individual lepidotrichia (bony ray) segments and at distal tips of developing zebrafish fins. It also apical growth zone regenerating However, so far there no functional evidence that addresses whether required for any aspect fin development or regeneration. In this study, we use a novel mutation evx1 to address this. We find not either outgrowth All fins form normally mutants, are significant changes length. contrast,...
Abstract Background Lbx/ladybird genes originated as part of the metazoan cluster Nk homeobox genes. In all animals investigated so far, both protostome and vertebrate Lbx1 were found to play crucial roles in neural muscle development. Recently however, additional Lbx with divergent expression patterns discovered amniotes. Early evolution vertebrates, two rounds whole genome duplication are thought have occurred, during which 4 generated. Which these maintained extant how their functions...
In mouse, Hedgehog (Hh) signalling is required for most ventral spinal neurons to form. Here, we analyse the cord phenotype of zebrafish maternal-zygotic smoothened (MZsmo) mutants that completely lack Hh signalling. We find V3 domain cells and motoneurons are lost, whereas medial floorplate still develops normally V2, V1 V0v form in normal numbers. This resembles mice both Gli repressor activity. Ventral progenitor transcription factors not expressed at 24 hpf MZsmo mutants. However, pMN,...
Polycystic kidney disease (PKD) proteins are trans-membrane that have crucial roles in many aspects of vertebrate development and physiology, including the organs as well left-right patterning taste. They can be divided into structurally-distinct PKD1-like PKD2-like usually one protein forms a heteromeric polycystin complex with protein. For example, PKD1 PKD2 mutations either these cause Autosomal Dominant Kidney Disease (ADPKD), which is most frequent potentially-lethal single-gene...
Within the vertebrate lineage, a high proportion of duplicate genes have been retained after whole genome duplication (WGD) events. It has proposed that many these became indispensable because ancestral gene function was divided between them. In addition, novel functions may evolved, owing to changes in cis-regulatory elements. Functional analysis PAX2/5/8 subfamily appears support at least first part this hypothesis. The collective role widely retained, but sub-functions differentially...
We provide the first analysis of how a segmentally reiterated pattern neurons is specified along anteroposterior axis vertebrate spinal cord by investigating zebrafish primary motoneurons are patterned. Two identified motoneuron subtypes, MiP and CaP, occupy distinct locations within ventral neural tube relative to overlying somites, express different genes innervate muscle territories. In all vertebrates examined so far, paraxial mesoderm-derived signals specify subpopulations in specific...
In the zebrafish, Fgf and Hh signalling assign anterior posterior identity, respectively, to poles of developing ear. Mis-expression fgf3 or inhibition results in double-anterior ears, including ectopic expression hmx3a. To understand how this pattern is established, we characterised transcriptional responses gain-of-signalling loss-of-signalling backgrounds. resulted rapid expansion otic markers, refining over time give duplicated pattern. Response was very different: initial...
The ability of the maximum-entropy method to determine accurate particle size distributions from small-angle scattering data is examined in detail. well known commercial software package MEMS YS2 has been used for core algorithm enable results be most generally applicable. Differences its reproduce number, mass and intensity simulated are presented. Results a maximum-entropy-method analysis experimental neutron self-consistency agreement with dynamic light data.