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.


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).

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.


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, luow@mail.med.upenn.edu>

Jingwen Niu, postdoc, Ph.D, niuj@mail.med.upenn.edu

Anna Vysochan, technician & lab manager, BS, vysochan@mail.med.upenn.edu