Overview

One of the most daunting problems of modem biology is to determine how a genome consisting of only ~30,000 genes drives the development of one of the most complex of organ systems – the mammalian brain. Most of the time – amazingly – the brain develops perfectly. When cells do not follow the proper developmental pathways, it leads to disorders of the developing central nervous system (CNS). These developmental brain disorders can have a clear genetic basis (e.g. forms of mental retardation and lissencephaly) or a far more complex etiology that involves multiple genes and environmental factors (e.g. autism, attention deficit disorder and schizophrenia).

The lab studies both single gene and more complex developmental disorders of the CNS. The research integrates the power of genomics, informatics and the mouse as an experimental model system to drive discovery about normal and abnormal brain development and to identify new therapies and interventions to improve outcomes for affected children.

Publications

Systems genetics of intravenous cocaine self-administration in the BXD recombinant inbred mouse panel
Psychopharmacology
DOI: 10.1007/s00213-015-4147-z
2016

RAAV-compatible MiniPromoters for restricted expression in the brain and eye
Molecular Brain
DOI: 10.1186/s13041-016-0232-4
2016

A novel and multivalent role of pax6 in cerebellar development
Journal of Neuroscience
DOI: 10.1523/JNEUROSCI.4385-15.2016
2016

The cerebellum and SIDS: Disordered breathing in a mouse model of developmental cerebellar purkinje cell loss during recovery from hypercarbia
Frontiers in Neurology
DOI: 10.3389/fneur.2016.00078
2016

Cerebellar contribution to higher and lower order rule learning and cognitive flexibility in mice
Neuroscience
DOI: 10.1016/j.neuroscience.2016.03.040
2016

CbGRiTS: Cerebellar gene regulation in time and space
Developmental Biology
DOI: 10.1016/j.ydbio.2014.09.032
2015

Kruppel-like factor 4 regulates granule cell Pax6 expression and cell proliferation in early cerebellar development
PLoS ONE
DOI: 10.1371/journal.pone.0134390
2015

The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome
PLoS Biology
DOI: 10.1371/journal.pbio.1002315
2015

Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells
Science
DOI: 10.1126/science.1259418
2015

Varied manifestations of persistent hyperplastic primary vitreous with graded somatic mosaic deletion of a single gene
Molecular Vision
2014

Glutamate dysfunction associated with developmental cerebellar damage: Relevance to autism spectrum disorders
Cerebellum
DOI: 10.1007/s12311-013-0541-4
2014

Molecular pathways underpinning ethanol-induced neurodegeneration
Frontiers in Genetics
DOI: 10.3389/fgene.2014.00203
2014

The effect of hemorrhage on the development of the postnatal mouse cerebellum
Experimental Neurology
DOI: 10.1016/j.expneurol.2013.11.010
2014

A promoter-level mammalian expression atlas
Nature
DOI: 10.1038/nature13182
2014

CAGE-defined promoter regions of the genes implicated in Rett Syndrome
BMC Genomics
DOI: 10.1186/1471-2164-15-1177
2014

Wls provides a new compartmental view of the rhombic lip in mouse cerebellar development
Journal of Neuroscience
DOI: 10.1523/JNEUROSCI.1330-14.2014
2014

The effects of pre- and post-natal nicotine exposure and genetic background on the striatum and behavioral phenotypes in the mouse
Behavioural Brain Research
DOI: 10.1016/j.bbr.2014.02.038
2014

Identification of genetic loci that modulate cell proliferation in the adult rostral migratory stream using the expanded panel of BXD mice
BMC Genomics
DOI: 10.1186/1471-2164-15-206
2014

Impaired Hypercarbic and Hypoxic Responses from Developmental Loss of Cerebellar Purkinje Neurons: Implications for Sudden Infant Death Syndrome
Cerebellum
DOI: 10.1007/s12311-014-0592-1
2014

Ethics challenges of transition from paediatric to adult health care services for young adults with neurodevelopmental disabilities
Paediatrics and Child Health (Canada)
2014

Use of the Expanded Panel of BXD Mice Narrow QTL Regions in Ethanol-Induced Locomotor Activation and Motor Incoordination
Alcoholism: Clinical and Experimental Research
DOI: 10.1111/j.1530-0277.2012.01865.x
2013

Dab2IP GTPase Activating Protein Regulates Dendrite Development and Synapse Number in Cerebellum
PLoS ONE
DOI: 10.1371/journal.pone.0053635
2013

Reorganization of circuits underlying cerebellar modulation of prefrontal cortical dopamine in mouse models of autism spectrum disorder
Cerebellum
DOI: 10.1007/s12311-013-0462-2
2013

Non-coding-regulatory regions of human brain genes delineated by bacterial artificial chromosome knock-in mice
BMC Biology
DOI: 10.1186/1741-7007-11-106
2013

Is autism a disease of the cerebellum?: An integration of clinical and pre-clinical research
Frontiers in Systems Neuroscience
DOI: 10.3389/fnsys.2013.00015
2013

Effects of stimulus salience on touchscreen serial reversal learning in a mouse model of fragile X syndrome
Behavioural Brain Research
DOI: 10.1016/j.bbr.2013.05.060
2013

Excessive activation of tissue plasminogen activator makes a mouse nervous
Proceedings of the National Academy of Sciences of the United States of America
DOI: 10.1073/pnas.1309965110
2013

Effects of age and strain on cell proliferation in the mouse rostral migratory stream
Neurobiology of Aging
DOI: 10.1016/j.neurobiolaging.2012.12.021
2013

The expression of HDAC1 and HDAC2 during cerebellar cortical development
Cerebellum
DOI: 10.1007/s12311-013-0459-x
2013

Consensus paper: Pathological role of the cerebellum in Autism
Cerebellum
DOI: 10.1007/s12311-012-0355-9
2012

Genome-wide microarray comparison reveals downstream genes of Pax6 in the developing mouse cerebellum
European Journal of Neuroscience
DOI: 10.1111/j.1460-9568.2012.08221.x
2012

19p13.2 microduplication causes a Sotos syndrome-like phenotype and alters gene expression
Clinical Genetics
DOI: 10.1111/j.1399-0004.2010.01615.x
2012

Gene Discovery: From Positional Cloning to Genomic Cloning
Gene Discovery for Disease Models
DOI: 10.1002/9780470933947.ch1
2012

Kainic acid-induced neuronal degeneration in hippocampal pyramidal neurons is driven by both intrinsic and extrinsic factors: Analysis of FVB/N¿C57BL/6 chimeras
Journal of Neuroscience
DOI: 10.1523/JNEUROSCI.6478-11.2012
2012

Linking Early Brain and Biological Development to Psychiatry
Journal of the Canadian Academy of Child and Adolescent Psychiatry
2011

Spatial and temporal requirements for huntingtin (Htt) in neuronal migration and survival during brain development
Journal of Neuroscience
DOI: 10.1523/JNEUROSCI.2774-11.2011
2011

Conserved and differential gene interactions in dynamical biological systems
Bioinformatics
DOI: 10.1093/bioinformatics/btr472
2011

The NeuroDevNet Vision
Seminars in Pediatric Neurology
DOI: 10.1016/j.spen.2011.02.007
2011

Fetal Alcohol Spectrum Disorders: Gene-Environment Interactions, Predictive Biomarkers, and the Relationship Between Structural Alterations in the Brain and Functional Outcomes
Seminars in Pediatric Neurology
DOI: 10.1016/j.spen.2011.02.006
2011

NeuroDevNet: A Canada Network of Centres of Excellence-To Realize a Vision by Effective Operations and Collaborative Mechanisms
Seminars in Pediatric Neurology
DOI: 10.1016/j.spen.2011.02.008
2011

Connecting the dots of the cerebro-cerebellar role in cognitive function: Neuronal pathways for cerebellar modulation of dopamine release in the prefrontal cortex
Synapse
DOI: 10.1002/syn.20960
2011

The genetic basis of adrenal gland weight and structure in BXD recombinant inbred mice
Mammalian Genome
DOI: 10.1007/s00335-011-9315-9
2011

Experimental Sey mouse chimeras reveal the developmental deficiencies of Pax6-null granule cells in the postnatal cerebellum
Developmental Biology
DOI: 10.1016/j.ydbio.2010.11.018
2011

Genotype-dependent effects of adolescent nicotine exposure on dopamine functional dynamics in the nucleus accumbens shell in male and female mice: A potential mechanism underlying the gateway effect of nicotine
Psychopharmacology
DOI: 10.1007/s00213-010-2159-2
2011

Introduction
Seminars in Pediatric Neurology
DOI: 10.1016/j.spen.2011.03.001
2011

Dopamine dynamics associated with, and resulting from, schedule-induced alcohol self-administration: Analyses in dopamine transporter knockout mice
Alcohol
DOI: 10.1016/j.alcohol.2010.12.006
2011

Inter-disciplinary research in the pediatric neurosciences: the NeuroDevNet model. Introduction.
Seminars in pediatric neurology
2011

Inherited neuroaxonal dystrophy in dogs causing lethal, fetal-onset motor system dysfunction and cerebellar hypoplasia
The Journal of comparative neurology
DOI: 10.1002/cne.22423
2010

Identification of a Chr 11 quantitative trait locus that modulates proliferation in the rostral migratory stream of the adult mouse brain
European Journal of Neuroscience
DOI: 10.1111/j.1460-9568.2010.07316.x
2010

Behavioral flexibility in a mouse model of developmental cerebellar Purkinje cell loss
Neurobiology of Learning and Memory
DOI: 10.1016/j.nlm.2010.05.010
2010

Phenotypic and genetic analysis of the cerebellar mutant tmgc26, a new ENU-induced ROR-alpha allele
European Journal of Neuroscience
DOI: 10.1111/j.1460-9568.2010.07330.x
2010

Foxn3 is essential for craniofacial development in mice and a putative candidate involved in human congenital craniofacial defects
Biochemical and Biophysical Research Communications
DOI: 10.1016/j.bbrc.2010.07.142
2010

Repetitive behavior and increased activity in mice with Purkinje cell loss: A model for understanding the role of cerebellar pathology in autism
European Journal of Neuroscience
DOI: 10.1111/j.1460-9568.2009.07073.x
2010

High-throughput behavioral phenotyping in the expanded panel of BXD recombinant inbred strains
Genes, Brain and Behavior
DOI: 10.1111/j.1601-183X.2009.00540.x
2010

Studies on the hippocampal formation: From basic development to clinical applications: Studies on schizophrenia
Progress in Neurobiology
DOI: 10.1016/j.pneurobio.2009.10.008
2010

A regulatory toolbox of MiniPromoters to drive selective expression in the brain
Proceedings of the National Academy of Sciences of the United States of America
DOI: 10.1073/pnas.1009158107
2010

Ethanol-induced hyperactivity is associated with hypodopaminergia in the 22-TNJ ENU-mutated mouse
Alcohol
DOI: 10.1016/j.alcohol.2009.04.006
2009

Next generation tools for high-throughput promoter and expression analysis employing single-copy knock-ins at the Hprt1 locus
Genomics
DOI: 10.1016/j.ygeno.2008.09.014
2009

Genetics of the hippocampal transcriptome in mouse: A systematic survey and online neurogenomics resource
Frontiers in Neuroscience
DOI: 10.3389/neuro.15.003.2009
2009

CAG repeat lengths = 335 attenuate the phenotype in the R6/2 Huntington's disease transgenic mouse
Neurobiology of Disease
DOI: 10.1016/j.nbd.2008.10.009
2009

Standards for the publication of mouse mutant studies
Genes, Brain and Behavior
DOI: 10.1111/j.1601-183X.2008.00438.x
2009

ENU induced single mutation locus on chr 16 leads to high-frequency hearing loss in mice
Genes and Genetic Systems
DOI: 10.1266/ggs.84.219
2009

Genetic mapping of vocalization to a series of increasing acute footshocks using B6.A consomic and B6.D2 congenic mouse strains
Behavior Genetics
DOI: 10.1007/s10519-008-9210-7
2008

Identification of a set of genes showing regionally enriched expression in the mouse brain
BMC Neuroscience
DOI: 10.1186/1471-2202-9-66
2008

Acute mild footshock alters ethanol drinking and plasma corticosterone levels in C57BL/6J male mice, but not DBA/2J or A/J male mice
Alcohol
DOI: 10.1016/j.alcohol.2008.05.001
2008

VAC14 nucleates a protein complex essential for the acute interconversion of PI3P and PI(3,5)P2 in yeast and mouse
EMBO Journal
DOI: 10.1038/emboj.2008.248
2008

Cerebellar modulation of frontal cortex dopamine efflux in mice: Relevance to autism and schizophrenia
Synapse
DOI: 10.1002/syn.20525
2008

An integrative genomics strategy for systematic characterization of genetic loci modulating phenotypes
Human Molecular Genetics
DOI: 10.1093/hmg/ddm089
2007

PolymiRTS Database: Linking polymorphisms in microRNA target sites with complex traits
Nucleic Acids Research
DOI: 10.1093/nar/gkl797
2007

A mouse model of Waardenburg syndrome type IV resulting from an ENU-induced mutation in endothelin 3
Pigment Cell Research
DOI: 10.1111/j.1600-0749.2007.00371.x
2007

Neurobehavioral mutants identified in an ENU-mutagenesis project
Mammalian Genome
DOI: 10.1007/s00335-007-9035-3
2007

Persistent hyperplastic primary vitreous due to somatic mosaic deletion of the Arf tumor suppressor
Investigative Ophthalmology and Visual Science
DOI: 10.1167/iovs.06-0765
2007

Wild-type cells rescue genotypically Math1-null hair cells in the inner ears of chimeric mice
Developmental Biology
DOI: 10.1016/j.ydbio.2007.02.028
2007

A transgenic mouse class-III ßtubulin reporter using yellow fluorescent protein
Genesis
DOI: 10.1002/dvg.20325
2007

R6/2 neurons with intranuclear inclusions survive for prolonged periods in the brains of chimeric mice
Journal of Comparative Neurology
DOI: 10.1002/cne.21515
2007

The requirement of Pax6 for postnatal eye development: Evidence from experimental mouse chimeras
Investigative Ophthalmology and Visual Science
DOI: 10.1167/iovs.06-1482
2007

Screening for ENU-Induced Mutations in Mice That Result in Aberrant Ethanol-Related Phenotypes
Behavioral Neuroscience
DOI: 10.1037/0735-7044.121.4.665
2007

Combining gene expression QTL mapping and phenotypic spectrum analysis to uncover gene regulatory relationships
Mammalian Genome
DOI: 10.1007/s00335-005-0172-2
2006

Identification of 17 hearing impaired mouse strains in the TMGC ENU-mutagenesis screen
Hearing Research
DOI: 10.1016/j.heares.2006.07.011
2006

Sustained attention in the mouse: A study of the relationship with the cerebellum
Behavioral Neuroscience
DOI: 10.1037/0735-7044.120.2.477
2006

Huntingtin inhibits caspase-3 activation
EMBO Journal
DOI: 10.1038/sj.emboj.7601445
2006

Progress in using mouse inbred strains, consomics, and mutants to identify genes related to stress, anxiety, and alcohol phenotypes
Alcoholism: Clinical and Experimental Research
DOI: 10.1111/j.1530-0277.2006.00125.x
2006

An ENU-induced mutation in Rs1h causes disruption of retinal structure and function
Molecular Vision
2005

Compartmentation of the reeler cerebellum: Segregation and overlap of spinocerebellar and secondary vestibulocerebellar fibers and their target cells
Neuroscience
DOI: 10.1016/j.neuroscience.2004.09.051
2005

Disruption of cerebellar granule cell development in the Pax6 mutant, Sey mouse
Developmental Brain Research
DOI: 10.1016/j.devbrainres.2005.09.005
2005

Enhanced Purkinje cell survival but compromised cerebellar function in targeted anti-apoptotic protein transgenic mice
Molecular and Cellular Neuroscience
DOI: 10.1016/j.mcn.2005.02.010
2005

The Tennessee Mouse Genome Consortium: Identification of ocular mutants
Visual Neuroscience
DOI: 10.1017/S0952523805225087
2005

Increased calbindin-D28k immunoreactivity in striatal projection neurons of R6/2 Huntington's disease transgenic mice
Neurobiology of Disease
DOI: 10.1016/j.nbd.2005.05.023
2005

Phenotype screening for genetically determined age-onset disorders and increased longevity in ENU-mutagenized mice
Age
DOI: 10.1007/s11357-005-4131-3
2005

A deletion causing spontaneous fracture identified from a candidate region of mouse chromosome 14
Mammalian Genome
DOI: 10.1007/s00335-004-2414-0
2005

A relationship between cerebellar Purkinje cells and spatial working memory demonstrated in a lurcher/chimera mouse model system
Genes, Brain and Behavior
DOI: 10.1111/j.1601-183x.2004.00067.x
2004

Implementing large-scale ENU mutagenesis screens in North America
Genetica
DOI: 10.1007/s10709-004-1436-6
2004

A genome end-game: Understanding gene function in the nervous system
Nature Neuroscience
DOI: 10.1038/nn0504-484
2004

Analysis of Cerebellar Development in math1 Null Embryos and Chimeras
Journal of Neuroscience
DOI: 10.1523/JNEUROSCI.3427-03.2004
2004

Large-scale mutagenesis of the mouse to understand the genetic bases of nervous system structure and function
Molecular Brain Research
DOI: 10.1016/j.molbrainres.2004.09.016
2004

Plans for HDBase - A research community website for Huntington's disease
Clinical Neuroscience Research
DOI: 10.1016/S1566-2772(03)00062-8
2003

Wild-Type Huntingtin Plays a Role in Brain Development and Neuronal Survival
Molecular Neurobiology
DOI: 10.1385/MN:28:3:259
2003

The cerebellum and spatial ability: Dissection of motor and cognitive components with a mouse model system
European Journal of Neuroscience
DOI: 10.1046/j.1460-9568.2003.02921.x
2003

Clonal Architecture of the Mouse Hippocampus
Journal of Neuroscience
2002

Developmental expression of PAM (protein associated with MYC) in the rodent brain
Developmental Brain Research
DOI: 10.1016/S0165-3806(02)00311-5
2002

Preliminary analysis of the mouse cerebellum proteome
Molecular Brain Research
DOI: 10.1016/S0169-328X(01)00333-3
2002

The renal glomerulus and vasculature in 'Aggregation' chimeric mice
Nephron
DOI: 10.1159/000049062
2002

Differential changes in striatal projection neurons in R6/2 transgenic mice for Huntington's disease
Neurobiology of Disease
DOI: 10.1006/nbdi.2002.0554
2002

Cellular localization and development of neuronal intranuclear inclusions in striatal and cortical neurons in R6/2 transgenic mice
Journal of Comparative Neurology
DOI: 10.1002/cne.10295
2002

Dissection of the cellular and molecular events that position cerebellar Purkinje cells: A study of the math1 null-mutant mouse
Journal of Neuroscience
2002

The community effect and Purkinje cell migration in the cerebellar cortex: Analysis of scrambler chimeric mice
Journal of Neuroscience
2002

Abnormalities in the functioning of adipocytes from R6/2 mice that are transgenic for the Huntington's disease mutation
Human Molecular Genetics
2001

Zona incerta: Substrate for contralateral interconnectivity in the thalamus of rats
Journal of Comparative Neurology
DOI: 10.1002/cne.1053
2001

Sequence interpretation: Functional annotation of mouse genome sequences
Science
DOI: 10.1126/science.1058244
2001

Neurons lacking huntingtin differentially colonize brain and survive in chimeric mice
Journal of Neuroscience
2001

Granule cells and cerebellar boundaries: Analysis of Unc5h3 mutant chimeras
Journal of Neuroscience
2000

Rescue of cerebellar granule cells from death in weaver NR1 double mutants
Journal of Neuroscience
1999

Extrinsic modulation of retinal ganglion cell projections: Analysis of the albino mutation in pigmentation mosaic mice
Developmental Biology
DOI: 10.1006/dbio.1999.9467
1999

Disrupted retinal development in the embryonic belly spot and tail mutant mouse
Developmental Biology
DOI: 10.1006/dbio.1998.9142
1999

Mapping genes that control brain size and neuron number: A QTL analysis of the mouse CNS and retina
FASEB Journal
1998

The cells and molecules that make a cerebellum
Trends in Neurosciences
DOI: 10.1016/S0166-2236(98)01313-7
1998

Novel receptor protein tyrosine phosphatase (RPTP¿) and acidic fibroblast growth factor (FGF-1) transcripts delineate a rostrocaudal boundary in the granule cell layer of the murine cerebellar cortex
Journal of Comparative Neurology
DOI: 10.1002/(SICI)1096-9861(19980222)391:4<444::AID-CNE3>3.0.CO;2-0
1998

Disabled-1 acts downstream of Reelin in a signaling pathway that controls laminar organization in the mammalian brain
Development
1998

Natural variation in neuron number in mice is linked to a major quantitative trait locus on Chr 11
Journal of Neuroscience
1998

Drain development, VIII: the reeler mouse.
The American journal of psychiatry
1998

Cerebellar mutant mice and chimeras revisited
Perspectives on Developmental Neurobiology
1997

Developmental expression of the GIRK family of inward rectifying potassium channels: Implications for abnormalities in the weaver mutant mouse
Brain Research
DOI: 10.1016/S0006-8993(97)00896-2
1997

Scrambler and yotari disrupt the disabled gene and produce a reeler- like phenotype in mice
Nature
DOI: 10.1038/39601
1997

Cerebellar disorganization characteristic of reeler in scrambler mutant mice despite presence of reelin
Journal of Neuroscience
1997

Decreased retinal ganglion cell number and misdirected axon growth associated with fissure defects in Bst/+ mutant mice
Investigative Ophthalmology and Visual Science
1997

meander tail acts intrinsic to granule cell precursors to disrupt cerebellar development: Analysis of meander tail chimeric mice
Development
1997

Birthdate and cell marker analysis of scrambler: A novel mutation affecting cortical development with a reeler-like phenotype
Journal of Neuroscience
1997

Genetic and environmental control of variation in retinal ganglion cell number in mice
Journal of Neuroscience
1996

Annexin IV is a marker of roof and floor plate development in the murine CNS
Journal of Comparative Neurology
DOI: 10.1002/(SICI)1096-9861(19960513)368:4<527::AID-CNE5>3.0.CO;2-6
1996

The weaver mutation of GIRK2 results in a loss of inwardly rectifying K+ current in cerebellar granule cells
Proceedings of the National Academy of Sciences of the United States of America
DOI: 10.1073/pnas.93.20.11191
1996

Analysis of gene action in the meander tail mutant mouse: Examination of cerebellar phenotype and mitotic activity of granule cell neuroblasts
Journal of Comparative Neurology
DOI: 10.1002/(SICI)1096-9861(19960429)368:2<304::AID-CNE10>3.0.CO;2-H
1996

Arbitrary primer PCR of dog DNA with estimates of average heterozygosity
Journal of Heredity
1996

Clonal architecture of the mouse retina
Progress in Brain Research
1996

Tune into the weaver channel
Nature Genetics
1995

Genetic control of retinal projections in inbred strains of albino mice
Journal of Comparative Neurology
DOI: 10.1002/cne.903540312
1995

Mapping the Bst mutation on mouse Chromosome 16: a model for human optic atrophy
Mammalian Genome
DOI: 10.1007/BF00356174
1995

Tune into the weaver channel
Nature Genetics
DOI: 10.1038/ng1095-107
1995

The annexins: Specific markers of midline structures and sensory neurons in the developing murine central nervous system
Journal of Comparative Neurology
DOI: 10.1002/cne.903520308
1995

Developmental regulation of various annexins in the embryonic palate of the mouse: Dexamethasone affects expression of annexin-1
Journal of Craniofacial Genetics and Developmental Biology
1995

Inhibition of migration of neural crest-derived cells by the abnormal mesenchyme of the presumptive aganglionic bowel of Is/Is mice: Analysis with aggregation and interspecies chimeras
Developmental Biology
1993

Reply
Trends in Neurosciences
DOI: 10.1016/0166-2236(93)90132-6
1993

Distribution of the blood-brain barrier in heterotopic brain transplants and its relationship to the lesions of EAE
Journal of Neuropathology and Experimental Neurology
1992

Lineage versus environment in embryonic retina: a revisionist perspective
Trends in Neurosciences
DOI: 10.1016/0166-2236(92)90181-7
1992

Structure of clonal and polyclonal cell arrays in chimeric mouse retina
Proceedings of the National Academy of Sciences of the United States of America
1992

Abnormalities in premigratory granule cells in the weaver cerebellum defined by monoclonal antibody OZ42
Anatomy and Embryology
DOI: 10.1007/BF00192209
1991

Expression of prostaglandin G H synthase (cyclooxygenase) during murine fetal thymic development
Cellular Immunology
DOI: 10.1016/0008-8749(91)90084-O
1991

Olivocerebellar fiber maturation in normal and lurcher mutant mice: Defective development in lurcher
Journal of Comparative Neurology
DOI: 10.1002/cne.902910308
1990

NCAM gene expression during the development of cerebellum and dentate gyrus in the mouse
Developmental Brain Research
DOI: 10.1016/0165-3806(90)90230-V
1990

Postnatal development of the wild-type and weaver cerebellum after embryonic administration of propylthiouracil (PTU)
Developmental Brain Research
DOI: 10.1016/0165-3806(90)90151-N
1990

Purkinje cell loss is due to a direct action of the weaver gene in Purkinje cells: evidence from chimeric mice
Developmental Brain Research
DOI: 10.1016/0165-3806(90)90237-S
1990

Development and death of external granular layer cells in the weaver mouse cerebellum: A quantitative study
Journal of Neuroscience
1989

The weaver granuloprival phenotype is due to intrinsic action of the mutant locus in granule cells: Evidence from homozygous weaver chimeras
Neuron
DOI: 10.1016/0896-6273(89)90045-7
1989

The mouse neurological mutant weaver maps within the region of chromosome 16 that is homologous to human chromosome 21
Genomics
DOI: 10.1016/0888-7543(89)90018-9
1989

Cell allocation in mammalian CNS formation: Evidence from murine interspecies aggregation chimeras
Neuron
DOI: 10.1016/0896-6273(89)90239-0
1989

Purkinje cell reduction in the reeler mutant mouse: A quantitative immunohistochemical study
Journal of Comparative Neurology
1989

Evidence for the transneuronal regulation of cerebellin biosynthesis in developing Purkinje cells
Journal of Neuroscience
1988

Description of Putative ribosomal RNAs with low abundance, developmental regulation, and the identifier sequence
Experimental Cell Research
DOI: 10.1016/0014-4827(88)90128-0
1988

Brain transplantation in genetic analysis of experimental allergic encephalomyelitis
Annals of the New York Academy of Sciences
1988

A highly abundant transcript in adult murine cerebellar granule cells contains repetitive sequences homologous to L1.
Journal of Neuroscience
1987

Brain Transplantation in the Study of Host Regulation of Susceptibility to Experimental Allergic Encephalomyelitis
Annals of the New York Academy of Sciences
DOI: 10.1111/j.1749-6632.1987.tb23717.x
1987

Heterotopic brain transplants in the study of experimental allergic encephalomyelitis
Experimental Neurology
DOI: 10.1016/0014-4886(87)90122-1
1987

Cell partitioning and mixing in the formation of the CNS: analysis of the cortical somatosensory barrels in chimeric mice
Developmental Brain Research
DOI: 10.1016/0165-3806(87)90002-2
1987

Cell partitioning and mixing in the formation of the CNS: analysis of the cortical somatosensory barrels in chimeric mice.
Brain Research
1987

Proto-oncogene c-myc is expressed in cerebellar neurons at different developmental stages.
The EMBO journal
1986

Performance of normal and neurological mutant mice on radial arm maze and active avoidance tasks
Behavioral and Neural Biology
DOI: 10.1016/S0163-1047(86)90696-5
1986

Longitudinal assessment of immunological abnormalities of mice with the autosomal recessive mutation, wasted
Federation Proceedings
1985

Longitudinal assessment of immunologic abnormalities of mice with the autosomal recessive mutation, 'wasted'
Journal of Immunology
1985

Regulation of axonal ingrowth into area dentata as studied by sequential, double intraocular brain tissue transplantation
Journal of Comparative Neurology
1984

Degree of hyperinnervation of area dentata by locus coeruleus in the presence of septum or entorhinal cortex as studied by sequential intraocular triple transplantation
Experimental Brain Research
DOI: 10.1007/BF00236291
1984

The neurological mutation staggerer is expressed in embryonic cerebellar transplants matured in the anterior eye chamber of normal mice
Neuroscience Letters
DOI: 10.1016/0304-3940(83)90412-3
1983

Granule cell as a site of gene action in the weaver mouse cerebellum: Evidence from heterozygous mutant chimeras
Journal of Neuroscience
1982

Nuclear morphology of ichthyosis mutant mice as a cell marker in chimeric brain
Developmental Biology
DOI: 10.1016/0012-1606(82)90313-X
1982

Immunohistochemical demonstration of plasticity in GABA neurons of the adult rat dentate gyrus
Brain Research
DOI: 10.1016/0006-8993(82)90116-0
1982

Anatomy of the isolated area dentata grown in the rat anterior eye chamber
Journal of Comparative Neurology
1982

Differential adrenergic neurotoxicity and Timm staining of heavy metals after intraocular injections of lead, cadmium or mercury
General Pharmacology: Vascular System
1981

Do neurotrophic interactions control synapse formation in the adult rat brain?
Brain Research
DOI: 10.1016/0006-8993(80)90616-2
1980

Axonal transport and axon sprouting in the adult rat dentate gyrus: An autoradiographic study
Neuroscience
DOI: 10.1016/0306-4522(80)90133-5
1980

The specificity of reactive synaptogenesis: A comparative study in the adult rat hippocampal formation
Brain Research
DOI: 10.1016/0006-8993(79)90962-4
1979

Induction of extensive fimbrial branching in the adult rat brain [18]
Nature
DOI: 10.1038/275064a0
1978

Electrophysiological analysis of the projection from the contralateral entorhinal cortex to the dentate gyrus in normal rats
Brain Research
DOI: 10.1016/0006-8993(76)90666-1
1976

Decreased temporal variability in hippocampal theta rhythms of cats administered methylphenidate
Behavioral Biology
DOI: 10.1016/S0091-6773(75)91129-3
1975

Anatomical evidence for a projection from the entorhinal cortex to the contralateral dentate gyrus of the rat
Experimental Neurology
DOI: 10.1016/0014-4886(75)90075-8
1975

Research

Gene-environment interactions in cerebellar development and function: insights into the origins of complex brain disorders
Fetal and perinatal events such as growth restriction and extreme prematurity exert a system-wide effect and falls under the framework of the developmental origins of health and disease. Our work will identify key transcriptomic and epigenomic changes that will suggest targets for intervention. We have used this approach with IVH and our initial work with IUGR. With the IUGR, we saw that the cerebellar epigenome had alterations in methylation. Treatment of the IUGR mice with a methyl-donor rich diet ameliorated the cerebellar phenotype and function of the IUGR pups, as well as altered the epigenome.

Mouse models for understanding neurodevelopmental disorders and interventions
We have 4 projects at various stages that have been designed to examine neurodevelopmental disorders: the loss of Purkinje cells in autism (one of the few documented neuroanatomic hallmarks of autism), a sequelae of extreme prematurity, intraventricular haemorrhage (IVH), and more recently, a mouse model for intrauterine growth restriction (IUGR) which is associated with adverse outcomes in humans; and a mouse model for brain insults coupled with inflammatory challenges that are risk factors in prematurity.

Novel genes involved in cerebellar development: discovery & validation
We use two large databases that we have built (www.cbgrits.org) or contributed to (fantom.gsc.riken.jp) that have painted a relatively complete transcriptome landscape of the cerebellum over developmental time and discover new genes and their relationship to other genes and gene pathways. We will validate the role of these genes in cerebellar development using techniques such as siRNA knockdown, genetically engineered knockouts and experimental chimeras.

Current Projects
My focus is on the cerebellum, a brain region involved in numerous levels of basic and higher function, and associated with developmental and behavioural disorders (eg, autism, ADHD, schizophrenia). My strength is in approaching neurodevelopment through the lens of genetics to (i) discover and validate genes involved in cerebellar development; (ii) create mouse models of perturbed cerebellar function to identify the earliest diagnostic signs of the disorder and develop evidence-based interventions; and (iii) understand the role of complex genetics, such as gene-environment interactions, in cerebellar development.

Honours & Awards

Canadian Research Chair in Developmental Neurogenetics Tier 1, 2007 - 2021

Scientific Director, NeuroDevNet NCE, 2009 – current

University of Florida, Applebaum Professorship, 2009

Research Group Members

Yuliya Badayeva, Laboratory Assistant
Rhea Beauchesne, Undergraduate Student
Chris Chen, Volunteer
Eric Chow, Laboratory Assistant
Brian Daly, Volunteer
Tanveer Dhandwar, Work Learn Student
Timonthy Frewin, Volunteer
Carol Gao, Volunteer
Ishita Gupta, Graduate Research Assistant
Jenna Langlois, Project Assistant
Ani Markarian, Volunteer
Castel Miguel Ramirez
Alanna Padula, WST Project Assistant
Jeffy Rajan Soundara Rajan, Graduate Research Assistant
Cheryl Tan, Work Learn Student
Joshua Wu, Volunteer
Ruisheng Xu, Undergraduate Research Assistant
Erin Yang, Student
Joanna Yeung, Postdoctoral Research Fellow
Pierre Zwiegers, Training Coordinator
Constance de Schaetzen, Undergraduate Student