|
Yuanhao James Li, Ph.D.Professor, Genetics and Genome Sciences
|
Degree | Institution | Major |
---|---|---|
B.S. | Zhongshan University | Biochemistry |
Ph.D. | University of Texas | Molecular Genetics |
Post-Graduate Training
Training | Institution | Specialty |
---|---|---|
Postdoctoral | HHMI in Skirball Institute of Biomolecular Medicine, New York University School of Medicine | Postdoctoral Fellow in the Developmental Genetics Program |
Awards
Name of Award/Honor | Awarding Organization |
---|---|
Individual National Research Service Award |
Name & Description | Category | Role | Type | Scope | Start Year | End Year |
---|---|---|---|---|---|---|
UCHC Biomedical Sciences graduate admissions committee | Education Committee | Member | UConn Health | University | 2013 | 2016 |
Animal Services Advisory Committee of UCHC | Advisory Committee | Member | UConn Health | University | 2007 | |
UCHC Biomedical Sciences Graduate Admissions Committee | Advisory Committee | Member | UConn Health | University | 2005 | 2007 |
Society for Developmental Biology | Professional/Scientific Organization | Member | External | National | ||
Society for Neuroscience | Professional/Scientific Organization | Member | External | National |
Research Interest My lab investigates how different brain cells, neurons and glia, are generated from neural stem cells and how brain cells form the neuronal network. These questions are fundamentally important to understand brain development. Knowledge of the developmental events will provide insight into the molecular and cellular mechanisms that underpin neurological diseases, such as Parkinson’s disease, autism, schizophrenia and depression. We combine several molecular and cellular approaches, including mouse genetics, in vitro assays, genomics, developmental neuroanatomy, and embryonic stem cells in our studies. Our on-going projects focus on two embryonic brain regions, the diencephalon (thalamus and habenular) and the mes-metencephalon (midbrain and cerebellum).
Molecular mechanisms of differentiation of habenular and thalamic neurons The thalamus and the associated habenula are derived from closely related progenitor domains. They together play important roles in modulating sensory, motor, cognitive and emotive functions. Habenular neurons receive inputs from the limbic system, and in turn connect and modulate the dopamine and serotonin systems of the midbrain and hindbrain. By contrast, thalamic neurons receive peripheral sensory inputs and project rostrally to the cortex. Abnormal formation and function of the habenula and thalamus have been implicated in brains disorders, such as depression, schizophrenia, sleeping disorders, and epilepsy. We recently identify key molecules that regulate the differentiation between habenular and thalamic neurons. Our long-term goal is to determine the molecular mechanisms that regulate thalamic and habenular identities and connectivities. Ultimately, this information will facilitate understanding the brain disorders resulting from abnormal formation and/or function of the thalamus and habenula.
Radial glial development in the cerebellum During cortical development of the cerebrum and cerebellum, radial glia cells in the ventricular zone provide guidance for neuronal migration and serve as stem cells for neurons and glial cells. Therefore, radial glial development is crucial for the formation of normal cortical architectonics. In contrast to the transient appearance of radial glia in the neocortex, cerebellar radial glia transform into specialized radial glia-like cells, called Bergmann glia. Bergmann glia maintain only the long basal processes and persist throughout the life of the animal. During cerebellar development, the Bergmann glial fibers provide scaffolds for migratory neurons. Interestingly, in both immature and mature cerebellum, Bergmann glia display hallmarks of neural stem cells. We recently discover the first known genetic mutation that specifically blocks Bergmann glial generation in mice. Analyses of the mutant mice also uncover a previously unappreciated function of Bergmann glia in the morphogenesis of the cerebellar cortex. Using whole genome transcriptome analysis, we identify putative genetic determinants for Bergmann glial generation. Remarkably, many of these Bergmann glia-specific genes have been implicated in the malignancy of glioma and medulloblastoma in adults and children, the most common primary malignant brain tumors in adults and children. These exciting findings will allow us to define the molecular and cellular mechanisms controlling Bergmann glial generation in the developing cerebellum. The acquired information would shed light on the molecular pathways leading to tumorigenesis in the brain.
Not accepting lab rotation students at this time
Journal Articles
-
Analogous mechanism regulating formation of neocortical basal radial glia and cerebellar Bergmann glia.
eLife 2017 May;6
-
Regulation of self-renewing neural progenitors by FGF-ERK signaling controls formation of the inferior colliculus.
Development (Cambridge, England) 2016 Aug;
-
Gbx2 is essential for maintaining thalamic neuron identity and repressing habenular characters in the developing thalamus.
Developmental biology 2015 Aug;407(1):26-39
-
T cell development involves TRAF3IP3-mediated ERK signaling in the Golgi.
The Journal of experimental medicine 2015 Jul;212(8):1323-36
-
The cochlear sensory epithelium derives from Wnt responsive cells in the dorsomedial otic cup.
Developmental biology 2015 Jan;399(1):177-87
-
Pax6 regulates the formation of the habenular nuclei by controlling the temporospatial expression of Shh in the diencephalon in vertebrates.
BMC biology 2014 Feb;12(13):13
-
Shp2-dependent ERK signaling is essential for induction of Bergmann glia and foliation of the cerebellum.
The Journal of neuroscience : the official journal of the Society for Neuroscience 2014 Jan;34(3):922-31
-
Differential BMP signaling controls formation and differentiation of multipotent preplacodal ectoderm progenitors from human embryonic stem cells.
Developmental biology 2013 Jul;379(2):208-20
-
Gbx2 regulates thalamocortical axon guidance by modifying the LIM and Robo codes.
Development (Cambridge, England) 2012 Dec;139(24):4633-43
-
Distinct developmental origins and regulatory mechanisms for GABAergic neurons associated with dopaminergic nuclei in the ventral mesodiencephalic region.
Development (Cambridge, England) 2012 Jul;139(13):2360-70
-
The lhx2 transcription factor controls thalamocortical axonal guidance by specific regulation of robo1 and robo2 receptors.
The Journal of neuroscience : the official journal of the Society for Neuroscience 2012 Mar;32(13):4372-85
-
Gbx2 plays an essential but transient role in the formation of thalamic nuclei.
PloS one 2012 Jan;7(10):e47111
-
Patterning and compartment formation in the diencephalon.
Frontiers in neuroscience 2012 Jan;666
-
Numerous isoforms of Fgf8 reflect its multiple roles in the developing brain.
Journal of cellular physiology 2011 Jul;226(7):1722-6
-
Gbx2 and Fgf8 are sequentially required for formation of the midbrain-hindbrain compartment boundary.
Development (Cambridge, England) 2011 Feb;138(4):725-34
-
The mouse homeobox gene Gbx2 is required for the development of cholinergic interneurons in the striatum.
The Journal of neuroscience : the official journal of the Society for Neuroscience 2010 Nov;30(44):14824-34
-
Fgf8b-containing spliceforms, but not Fgf8a, are essential for Fgf8 function during development of the midbrain and cerebellum.
Developmental biology 2010 Feb;338(2):183-92
-
Fgf8b, but not Fgf8a, is essential for Fgf8 signaling in the development of the mid-hindbrain.
Dev Biol 2010 Jan;338183-192
-
Misexpression of Gbx2 throughout the mesencephalon by a conditional gain-of-function transgene leads to deletion of the midbrain and cerebellum in mice.
Genesis (New York, N.Y. : 2000) 2009 Oct;47(10):667-73
-
Transcription factor Gbx2 acts cell-nonautonomously to regulate the formation of lineage-restriction boundaries of the thalamus.
Development (Cambridge, England) 2009 Apr;136(8):1317-26
-
Distinct functions of the major Fgf8 spliceform, Fgf8b, before and during mouse gastrulation.
Development (Cambridge, England) 2007 Jun;134(12):2251-60
-
Structural basis by which alternative splicing modulates the organizer activity of FGF8 in the brain.
Genes & development 2006 Jan;20(2):185-98
-
New regulatory interactions and cellular responses in the isthmic organizer region revealed by altering Gbx2 expression.
Development (Cambridge, England) 2005 Apr;132(8):1971-81
-
General method for the modification of different BAC types and the rapid generation of BAC transgenic mice.
Genesis (New York, N.Y. : 2000) 2004 Jan;38(1):39-50
-
FGF17b and FGF18 have different midbrain regulatory properties from FGF8b or activated FGF receptors.
Development (Cambridge, England) 2003 Dec;130(25):6175-85
-
Changing requirements for Gbx2 in development of the cerebellum and maintenance of the mid/hindbrain organizer.
Neuron 2002 Sep;36(1):31-43
-
Otx2 and Gbx2 are required for refinement and not induction of mid-hindbrain gene expression.
Development (Cambridge, England) 2001 Dec;128(24):4979-91
-
Sequence and genomic organization of the mouse Lim1 gene.
Mammalian genome : official journal of the International Mammalian Genome Society 1999 May;10(5):444-6
-
Esx1 is an X-chromosome-imprinted regulator of placental development and fetal growth.
Nature genetics 1998 Nov;20(3):309-11
-
Esx1, a novel X chromosome-linked homeobox gene expressed in mouse extraembryonic tissues and male germ cells.
Developmental biology 1997 Aug;188(1):85-95
Reviews
-
The Molecular Pathway Regulating Bergmann Glia and Folia Generation in the Cerebellum.
Cerebellum (London, England) 2017 Dec;
Title or Abstract | Type | Sponsor/Event | Date/Year | Location |
---|---|---|---|---|
Bergmann Glia Development, Genesis and Differentiation | Talk | The 8th International Symposium of the Society for Research on the Cerebell | 2017 | Winnipeg, Manitoba , Canada |
Shp2-dependent ERK signaling is essential for induction of Bergmann glia and foliation of the cerebellum | Panel Discussion | 2014 | Ventura, CA | |
Analysis of the development of the mouse inner ear using Gbx2 as a guide. | Poster | Society for Neuroscience Annual Meeting | 2008 | Washington, DC |
Cassette Exchange”: a Cre-loxP mediated recombination method for efficient generation of stable transgenic human embryonic stem cell lines. | Poster | Annual Connecticut Stem Cell Technology Symposium | 2008 | Farmington, CT |
Gbx2-dependent program regulates axon guidance of the thalamocortical projections. | Poster | Gordon Conference on Neural Development | 2008 | Newport, RI |
Gbx2 and Fgf8 are sequentially required for formation of the mid-hindbrain compartment boundary. | Poster | Society For Developmental Biology, 67st Annual Meeting | 2008 | Philadelphia, PA |
Gbx2-dependent program regulates axon guidance of the thalamocortical projections. | Poster | Northeast Regional Developmental Biology Meeting | 2007 | Northeast, USA |
Fgf8 function is orchestrated by different Fgf8 splice variants. | Poster | Gordon Conference on Fibroblast, Growth Factors In Development & Disease | 2006 | Ventura, CA |
Fgf8 function is orchestrated by different Fgf8 splice variants. | Poster | Development Biology, Gordon Research Conferences | 2005 | New Hampshire |
Expressing Gbx2 in rhombomere 4 in Gbx2 mutants rescues rhombomere 3 and causes deletion of the posterior midbrain. | Poster | Development Biology, Gordon Research Conferences | 2003 | New Hampshire |
Temporal requirements for Gbx2 in cerebellar development. | Poster | Society For Developmental Biology, 61st Annual Meeting | 2002 | New Hampshire |
Genetic analysis of Otx2 and Gbx2 function in mid-hindbrain development. | Poster | 2001 Development Biology, Gordon Research Conferences | 2001 | New Hampshire |