Section: Rotations

Tzumin Lee, Ph.D.,M.D.

Academic Role: Associate Professor

Faculty Appointment(s) In:
   Neurobiology

Other Affiliation(s):
   Program in Neuroscience

Rotation Projects

Project I.  Molecular genetic analysis of neuronal morphogenesis
      Using MARCM (Mosaic Analysis with a Repressible Cell Marker)-based genetic mosaic techniques, we have been systematically examining complex neuronal developmental processes with unprecedented single-cell resolution. The MARCM system further allows us to elucidate the molecular mechanisms underlying any observed developmental phenomenon, via isolation of mutations that disrupt normal development of homozygous mutant neurons in heterozygous brains.  Thanks to MARCM, we have demonstrated that the Drosophila Dscam (Down Syndrome Cell Adhesion Molecule) is specifically involved in mediating divergent segregation of sister branches during bifurcation of axons.  In addition, characterization of mutations that block pruning of larval stage-specific neurites during metamorphosis has led to discovery of TGF- 's functions in neural circuit remodeling.  We are in the process of identifying additional genes required for formation and remodeling of neural circuits and will further investigate the neuronal morphogenetic functions of such newly identified genes.

Project II.  Roles of Dscam Diversity in the Drosophila Brain
      Drosophila Dscam encodes numerous isoforms and is widely required for neuronal morphogenesis.  However, evidence is lacking for involvement of distinct Dscam isoforms in different neuronal morphogenetic processes.  Several independent lines of research are being pursued to determine roles of Dscam diversity in the Drosophila brain.  For instance, various subsets of exon alternatives have been removed in several new Dscam alleles, phenotypic analysis of which is ongoing in diverse model neurons; and various engineered genomic constructs, which encode different small subsets of Dscam isoforms, are being characterized for their abilities to rescue distinct Dscam loss-of-function phenotypes.  The immediate goal is to identify systematically various neuronal developmental defects that specifically result from partial or complete loss of Dscam diversity.

Project III.  Molecular genetic analysis of neuronal structural plasticity
      Functional neural circuits are highly plastic.  We study neural plasticity in the Drosophila olfactory system, where great structural plasticity exists and detailed neuronal connections are known.  We have been investigating plasticity of the olfactory topographic map in the antennal lobe using two independent binary transcriptional systems.  Fusing LexA with VP16 or the GAL4 transactivating domain (GAD), we obtained both GAL80-suppressible and GAL80-insensitive transcriptional factors that can efficiently drive expression of lexA operator (lexAop)-controlled transgenes in vivo.  In conjunction with GAL4/UAS, LexA::VP16/lexAop permits ectopic expression of dominant transgenes followed by detailed analysis of phenotypes across synapses.  Interestingly, LexA::VP16-governed expression of activated CaMKII in olfactory receptor neurons non-autonomously affects GAL4-marked projection neurons' glomerular innervation patterns in the antennal lobes.  We are currently dissecting its underlying cellular/molecular mechanisms, hoping to shed new light on plasticity of neural circuits.

Project IV.  Glia development and neuron-glia interactions
      Despite glia's essential roles in formation of the adult Drosophila brain, post-embryonic development of glia is poorly understood.  MARCM systems label cells based on lineage and birth timing, permitting systematic analysis of cell proliferation patterns in complex tissues.  Using repo-LexA::GAD in MARCM, we demonstrate that many CNS glial cells are generated after embryogenesis.  Preliminary MARCM analysis of larval-born glial cells suggest region-specific temporal regulation of post-embryonic gliogenesis as well as possible involvement of various types of blast cells in post-embryonic gliogenesis.  To characterize neurogenesis and gliogenesis at the same time, we recently developed "dual-expression-control" MARCM that permits simultaneous but differential labeling of GAL80-minus neurons and glial cells in intact fly brains.  Initial lineage analysis suggests presence of neuroglioblasts in the developing optic lobes but reveals no production of glia by post-embryonic MB neuronal precursors.  Comprehensive lineage analysis using dual-expression-control MARCM will further facilitate genetic mosaic studies on neurons, glial cells, and their dynamic interactions.

Office: 704
Phone: 508.856.7866
E-mail: Tzumin.Lee@umassmed.edu

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