Soo-Kyung Lee

Transcriptional regulatory network in CNS development

Unravelling the processes that generate the numerous neuronal subtypes and establish their appropriate connections to form a functional CNS is one of the main challenges in neuroscience today. Particularly, decoding the transcriptional regulatory network responsible for neuronal subtype specification is a fundamental step toward understanding CNS development and advancing methods to generate specific neurons in regenerative medicine.

Our goal is to develop a comprehensive map of the complex gene regulatory networks that direct cell-fate specification and assembly of neuro-circuits. Our major model systems include the spinal cord, which consists of distinct classes of neurons to assemble motor and sensory circuits, and the arcuate nucleus of the hypothalamus, which forms a core neuro-circuitry that mediates actions of peripheral adiposity signals, leptin and insulin, for energy balance. To achieve our goals, we dissect multiple layers of gene regulatory steps that render neuronal cell-fate specification, taking the following steps: to define transcription complexes specifying each neuronal population, to identify their downstream effector genes conferring unique cell-identity, to understand the epigenetic strategy orchestrating timely changes on gene transcription, to uncover the molecular mechanism by which the peripheral cues modulate neuronal gene expression, and to generate specific neuronal subtypes from stem cells by applying the developmental gene regulatory strategy that we define. Our study will eventually contribute to the design of a rational strategy to repair damaged neurons and to treat metabolic disorders in the human.

Having pioneered combinatorial transcription code studies in spinal cord development over the past few years, we have developed many molecular tools and animal model systems that enable us to explore critical layers of transcriptional regulation, such as epigenetic control, and that are applicable to investigating other areas of the CNS. We are employing combined approaches of mouse genetics and chick embryology to take advantage of their complementary strengths as experimental systems. In addition, we are utilizing embryonic stem cells extensively and biochemical and molecular methods to dissect the development of spinal and hypothalamic neurons.

Selected Publications

Lee SK, Pfaff SL (2001) Transcriptional networks regulating neuronal identity in the developing spinal cord. Nature Neuroscience 4:1183-1191.

Thaler JP*, Lee SK*, Jurata LW*, Gill GN, Pfaff SL (2002) LIM factor Lhx3 contributes to the specification of motor neuron and interneuron identity through cell-type-specific protein-protein interactions. Cell 110:237-249. (*Equal contribution)

Lee SK, Pfaff SL (2003) Synchronization of neurogenesis and motor neuron specification by direct coupling of bHLH and homeodomain transcription factors. Neuron 38:731-745.

Lee SK, Lee B, Ruiz EC, Pfaff SL (2005) Olig2 and Ngn2 function in opposition to modulate gene expression in motor neuron progenitor cells. Genes and Development 19:282-294.

Yeo M*, Lee SK*, Lee B, Ruiz EC, Pfaff SL, Gill GN (2005) Small CTD phosphatases function in silencing neuronal gene expression. Science 307:596-600. (*Equal contribution)

Visvanathan J, Lee S, Lee B, Lee JW, Lee SK (2007) The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development. Genes and Development 21:744-749.

Lee S, Lee B, Joshi K, Pfaff S, Lee JW, Lee SK (2008) A regulatory network to segregate the identity of neuronal subtypes. Developmental Cell 14:877-889.

Joshi K, Lee S, Lee B, Lee JW, Lee SK (2009) LMO4 controls the balance between excitatory and inhibitory spinal V2 interneurons. Neuron 61:839-851.

Lee S, Lee B, Lee JW, Lee SK (2009) Retinoid signaling and neurogenin2 function are coupled for the specification of spinal motor neurons through a chromatin modifier CBP. Neuron 62:641-654.

Contact Information

Soo-Kyung Lee, Ph.D.

Department of Molecular and Human Genetics

Department of Molecular and Cellular Biology

Baylor College of Medicine

One Baylor Plaza S840

Houston, Texas 77030, U.S.A.

Lab website

Tel: (713) 798-8524

Fax: (713) 798-8967

E-mail: sklee@bcm.edu