Faculty

Curriculum Vitae

• B.A., Biochemistry – University of California, Berkeley (1991-1994)
• Ph.D., Cell and Developmental Biology – University of Illinois, Urbana-Champaign (1996-2002)
• Postdoc, Physiology – University of California, San Francisco (2002-2007)
• Assistant Professor, Molecular and Cellular Pharmacology – University of Miami Miller School of Medicine (October 2007)

Research Interests

Our laboratory is using the fruit fly Drosophila melanogaster to study the molecular and cellular mechanisms that regulate dendrite morphogenesis and neural connectivity.

Each neuronal cell type is endowed with a unique dendritic architecture. How a neuron elaborates its dendritic arbor is critical for proper neural connectivity and in large part determines the way a neuron integrates and processes synaptic or sensory inputs. Therefore, dendrite morphology is an important determinant of neuronal function. Although a number of extrinsic and intrinsic factors have been identified that regulate dendrite development, relatively little is known about how different types of neurons acquire their type-specific dendrite morphologies.

The peripheral nervous system (PNS) of Drosophila provides an ideal model system to investigate the molecular mechanisms that regulate patterning of the dendritic arbor; dendrites of PNS neurons can be directly visualized in live animals and can be studied using well-established Drosophila genetic techniques. The Drosophila PNS contains many different types of neurons including the dendritic arborization (da) neurons, which can be subdivided into four distinct classes (I–IV) based on their dendrite morphology and increasing dendritic branching complexity (Figure 1). Each of the da neurons exhibits stereotypical dendritic arbors, facilitating the systematic analysis of dendritic morphogenesis of individual neuronal cell types.

Figure 1.Tracings of representative class I, class II, class III, and class IV dendritic arborization (da) neurons in the peripheral nervous system of Drosophila.

From a genetic screen for regulators of dendrite development, we found the spineless (ss) gene to be critical for the diversification of dendrite complexity. Spineless, a homologue of the mammalian aryl hydrocarbon (dioxin) receptor (Ahr), was previously identified as a member of a family of transcription factors that contain the basic helix-loop-helix (bHLH)-PAS domain. Mammalian Ahr binds the environmental toxin dioxin, which can induce a broad range of toxic effects including teratogenesis, immunosuppression, and tumor promotion. Fetal exposure to dioxin can cause a range of cognitive and behavioral defects, possibly due to dioxin action via Ahr in the brain. In Drosophila, ss acts cell-autonomously to regulate the morphological diversity of dendrites in all classes of da neurons. Remarkably, ss exerts diametrically opposing functions in different classes of da neurons to limit branching complexity in neurons that normally possess simple dendrites, but to promote the formation of higher-order branches in neurons that normally elaborate more complex dendritic arbors. In the absence of normal ss function, different classes of da neurons elaborate dendrites with similar morphologies (Figure 2), suggestive of the hypothesis that ss may act to convert a dendrite ‘default state’ to different complexities for different neurons in the nervous system.

Figure 2. Class I, class II, and class III da neurons exhibit similar dendrite arborization patterns in spineless mutant clones.

Our work on spineless provides an entry point for the study of a novel class of regulators of dendrite development that have opposing functions in different neuronal cell types. Our laboratory is investigating the molecular mechanisms that control the diversification of dendrite complexity of different neuronal cell types by addressing the following: 1) How is Ss expression regulated in different types of neurons and how does differential regulation of Ss lead to diametrically opposing functions in different cell types; 2) What are the downstream effectors through which ss controls dendritic morphogenesis in individual cell types; and 3) What other novel genetic pathways contribute to the diversification of the dendritic arbor. These studies will help us understand the molecular mechanisms through which Ss controls dendrite diversity and allow us to identify novel genes that are critical for proper dendrite morphogenesis.

Recent Publications

Parrish, J.Z., Emoto K., Kim, M.D. , and Jan, Y.N. (2007). Mechanisms that regulate establishment, maintenance, and remodeling of dendritic fields. Annual Review of Neuroscience , 30:399-423.

Kim, M.D. , Jan, L.Y., and Jan, Y.N. (2006). The bHLH-PAS protein Spineless is necessary for the diversification of dendrite morphology of Drosophila dendritic arborization neurons. Genes & Development, 20:2806-2819. (Featured in Perspectives in Genes & Development, 20:2773-2778)

Parrish, J.Z.*, Kim, M.D.*, Jan, L.Y., and Jan, Y.N. (2006). Genome-wide analyses identify transcription factors required for proper morphogenesis of Drosophila sensory neuron dendrites. Genes & Development, 20:820-835. (Featured in Leading Edge in Cell, 125(2):205 and in Genome Biology, 7:225) * authors contributed equally

Kim, M.D. , Kamiyama, D., Kolodziej, P., Hing, H., and Chiba, A. (2003). Isolation of Rho GTPase effector pathways during axon development. Developmental Biology, 262:282-293.

Kim, M.D. , Kolodziej, P., and Chiba, A. (2002). Growth cone pathfinding and filopodial dynamics are mediated separately by Cdc42 activation. Journal of Neuroscience, 22:1794-1806.