Perelman School of Medicine at the University of Pennsylvania

Department of Neuroscience

Wenqin Luo, M.D, Ph.D

faculty photo
Associate Professor of Neuroscience
Associate Professor of Institute for Regenerative Medicine (IRM), University of Pennsylvania School of Medicine
Department: Neuroscience
Graduate Group Affiliations

Contact information
University of Pennsylvania
Department of Neuroscience
3610 Hamilton Walk
145 Johnson Pavilion
Philadelphia, PA 19104
Office: 215-573-7281
Lab: 215-573-7275
MD (Medicine)
Hunan Medical University, 1996.
MS (Molecular Biology and Biochemistry)
Peking Union Medical College, 1999.
PhD (Neuroscience)
Johns Hopkins University School of Medicine, 2005.
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Description of Research Expertise

Research Interests: Development and Function of Mammalian Mechanosensory Dorsal Root Ganglion (DRG) Neurons

Keywords: Development, Function, Touch Sensation, DRG, Mouse Genetics

Research Details:

The ability to sense the external world is critical for both survival and propagation of an organism. In accordance with that, vertebrates have developed highly specified sensory organs and parallel afferent pathways to sense different stimuli. A central question in sensory neurobiology is how different types of sensory neurons acquire their functional properties and form distinct circuits during development. The mammalian dorsal root ganglion (DRG) is a good model system to address this issue because primary somatosensory DRG neurons have greatly diversified functions, subsets of which respond to body position, touch, temperature, itch and pain. In addition, DRG neurons are distinct with respect to their soma sizes, physiological properties, axonal morphologies and expression of molecular markers. Interestingly, even though cell bodies of different functional groups of DRG neurons are intermingled with each other, they innervate different layers of the spinal cord centrally (Figure 1) and project to distinct peripheral targets, clearly suggesting the use of parallel processing circuits.

Figure 1Figure 1. Laminar specific projections of different types of DRG neurons into spinal cord. Small-diameter temperature-, itch-, and pain-sensing neurons (nociceptors, red and green) innervate layer I and II, middle-diameter mechanosensitive Aδ fibers (Down (D) hair cells, light purple) innervate layer IIi and IIIo, large-diameter mechanosensitive Aβ fibers (mechanore-ceptors, orange and purple) innervate layer III through V, and large-diameter Aα body-position-sensing neurons (propriocep-tors, blue) innervate layer V through VII and IX.

Touch or mechanosensation is one of the most fundamental sensory modalities. Without "touch-sensing" neurons, we won't be able to sense a hug, a kiss, a summer breeze, or a particular texture. One the other hand, touch sensation is also the least understood sensory modality at the molecular and cellular level in mammals. At present, it is a stunning puzzle of which type of DRG neurons is responsible for the aforementioned different form of touch sensation, given most DRG neurons are mechanosensitive. Moreover, the molecular identities of the protein or protein com-plexes that directly detect mechanical forces remain elusive.

Among all mechanosensory DRG neurons, a small percentage of them are classic "mecha-noreceptors" (Figure 2), which are fast conducting (Aβ fiber), have large soma sizes, form specified peripheral end organs, and function in tactile and form discrimination. Mechanoreceptors are either rapidly- (RA) or slowly-adapting (SA) based on how quickly they habituate to sustained stimuli. Re-cently, using a novel genetic labeling technique, I discovered that a small population of DRG neurons that arise early in development and express the receptor tyrosine kinase Ret (early Ret+ neurons) de-velop into RA mechanoreceptors. These neurons form Pacinian corpuscles, Meissner corpuscles, and longitudinal lanceolate endings in the periphery, innervate layer III through V of the spinal cord, and terminate in the dorsal column nuclei of the brainstem in a modality specific pattern (Luo et al., Neuron, 2009).

Figure 2
Figure 2. Mechanosensory End Organs in the Skin.
To reveal molecular mechanisms that control functional diversity and circuit formation of different types of mechanosensory DRG neurons, I have focused on the roles of Ret signaling during development of non-peptidergic nociceptors, which mediate mechanical pain sensation, and RA mechanoreceptors. Ret is the signaling receptor for GDNF-like family ligands (GFLs), and requires a GPI-linked GFRα co-receptor to bind GFLs (Figure 3). Ret signaling attracted my attention because Ret is expressed in about 60% of adult mouse DRG neurons and functional GFRα1-3 are expressed in unique patterns in developing DRG neurons. Using mouse genetic models and a combination of cellular and molecular techniques, I found that Ret signaling plays distinct roles in non-peptidergic nociceptors and RA mechanoreceptors, although they both express high level of Ret and its co-receptor GFRα2. The development of non-peptidergic nociceptors is controlled by a hierarchical NGF and Ret signaling cascade. Ret signaling in these neurons is required for the acquisition of normal cell size, GPCR and TRP channel expression, epidermal innervation, and postnatal TrkA extinction, but not for the establishment of their central projections (Luo et al., Neuron, 2007). On the other hand, Ret signaling in RA mechanoreceptors is required for the initial development, but not maintenance of Pacinian corpuscles and establishment of proper central projections of most, if not all, RA mecha-noreceptors (Luo et al., Neuron, 2009). Taken together, my results demonstrate how Ret signaling controls functional properties and the assembly of two different classes of mechanosensory DRG neurons by altering the temporal and spatial expression patterns of its signaling components.

Figure 3
Figure 3. Ret signaling and three populations of Ret+ DRG neurons. A. Ret, ligands, and its co-receptors (adapted from Airaksinen et al., 2002, Nature Reviews Neurosci-ence) B. Three popula-tions of Ret+ DRG neu-rons based on their devel-opmental history and co-receptor expression.

In my lab, we will use a combination of molecular and cellular techniques, mouse genetic tools, and physiological recordings to focus on the following questions: 1. What are molecular mechanisms to direct the development of RA mechanoreceptors? 2. What are the molecular basis endowing the RA mechanroeceptors with rapidly adapting and mechanosensitive properties? 3. What are the de-velopmental origins of other types of mechanosensory neurons and their unique functions in different forms of touch sensation? Taken together, work from my lab will lead to a better understanding of the development of mechanosensory circuits, the mechanisms of mechanosensory transduction, and the cellular and molecular basis of the sense of touch.

Rotation Projections:

Lab Personnel:

Wenqin Luo, PI, M.D. & Ph.D,>

Jingwen Niu, postdoc, Ph.D,

Anna Vysochan, technician & lab manager, BS,

Selected Publications

Janardhan P. Bhattarai, Mary Schreck, Andrew H. Moberly, Wenqin Luo, Minghong Ma: Aversive Learning Increases Release Probability of Olfactory Sensory Neurons Current Biology Dec 2019.

Huasheng Yu, Tianjun Zhao, Simin Liu, Qinxue Wu, Omar Johnson, Zhaofa Wu, Zihao Zhuang, Yaocheng Shi, Luxin Peng, Renxi He, Yong Yang, Jianjun Sun, Xiaoqun Wang, Haifeng Xu, Zheng Zeng, Peng Zou, Xiaoguang Lei, Wenqin Luo*, Yulong Li* (co-corresponding author): MRGPRX4 is a bile acid receptor for human cholestatic itch. eLIFE September 2019.

Ishmail Abdus-Saboor, Nathan T. Fried1, Mark Lay, Kathryn Swanson, Roman Fischer, Justin Burdge, Jessica Jones, Peter Dong, Weihua Cai, Xinying Guo, Yuan-Xiang Tao, John Bethea, Minghong Ma, Xinzhong Dong, Long Ding, Wenqin Luo: A Mouse Pain Scale: Assessment of Pain Sensation in Mice Using Sub-second Behavioral Mapping and Statistical Modeling. Cell Reports Aug 2019.

Arthi Prabhakar , Dragan Vujovic , Lian Cui , William Olson , Wenqin Luo : Leaky expression of channelrhodopsin-2 (ChR2) in Ai32 mouse lines. PLOS ONE 14(3), March 2019.

Wang C, Gu L, Ruan Y, Geng X, Xu M, Yang N, Yu L, Jiang Y, Zhu C, Yang Y, Zhou Y, Guan X, Luo W, Liu Q, Dong X, Yu G, Lan L, Tang Z.: Facilitation of MrgprD by TRP-A1 promotes neuropathic pain. FASEB J. Jan 2019.

Olson W., Luo W.: Somatotopic Organization of Central Arbors from Nociceptive Afferents Develops Independently of Their Intact Peripheral Target Innervation. Journal of Comparative Neurology September 2018.

Kim Kridsada, Jingwen Niu, Zhiping Wang, Parthiv Haldipur, Long Ding, Jian J. Li, Anne G. Lindgren, Eloisa Herrera, Gareth M. Thomas, Victor V. Chizhikov, Kathleen J. Millen, Wenqin Luo: Roof Plate-Derived Dorsal Midline Radial Glial-like Cells Promote Longitudinal Ascending Axon Growth of Rapidly Adapting Mechanoreceptors during Development Cell Reports June 2018.

Andrew H. Moberly, Mary Schreck, Janardhan Bhattarai, Larry Zweifel, Wenqin Luo, and Minghong Ma : Olfactory inputs modulate respiration-related rhythmic activity in the prefrontal cortex and freezing behavior. Nature Communication April 2018.

Nadia Parmhans, Szilard Sajgo, Jingwen Niu, Wenqin Luo, Tudor Constantin Badea: Characterization of Retinal Ganglion Cell, Horizontal Cell, and Amacrine Cell Types Expressing the Neurotrophic Receptor Tyrosine Kinase Ret. Journal of Comparative Neurology March 2018.

William Olson, Ishmail Abdus-Saboor, Lian Cui, Justin Burdge, Tobias Raabe, Minghong Ma, Wenqin Luo: Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors. eLife Oct 2017.

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Last updated: 07/05/2020
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