Qiufu Ma

Qiufu Ma
Westlake University

About

99
Publications
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11,647
Citations
Citations since 2017
16 Research Items
3994 Citations
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20172018201920202021202220230200400600800
20172018201920202021202220230200400600800
20172018201920202021202220230200400600800
Introduction
In 2022,, after spending 24 years at Harvard Medical School, I moved my lab to Westlake University, Hangzhou, China. My lab has been mapping spinal pain pathways. In recent years, we started to work on the neuroanatomical basis behind acupuncture practice.
Skills and Expertise

Publications

Publications (99)
Article
Visceral pain is among the most prevalent and bothersome forms of chronic pain, but their transmission in the spinal cord is still poorly understood. Here, we conducted focal colorectal distention (fCRD) to drive both visceromotor responses (VMRs) and aversion. We first found that spinal CCK neurons were necessary for noxious fCRD to drive both VMR...
Preprint
Visceral pain is among the most prevalent and bothersome forms of chronic pain, but their transmission in the spinal cord is still poorly understood. Here we used a focal colorectal distention (fCRD) method to drive visceromotor responses (VMRs) plus affective pain-indicative aversive learning. We first found that spinal CCK neurons were necessary...
Article
Acupuncture has been practiced for more than 2000 years in China and now all over the world. One core idea behind this medical practice is that stimulation at specific body regions (acupoints) can distantly modulate organ physiology, but the underlying scientific basis has been long debated. Here, I summarize evidence supporting that long-distant a...
Article
Somatosensory afferents are traditionally classified by soma size, myelination, and their response specificity to external and internal stimuli. Here, we propose the functional subdivision of the nociceptive somatosensory system into two branches. The exteroceptive branch detects external threats and drives reflexive-defensive reactions to prevent...
Article
Full-text available
Somatosensory autonomic reflexes allow electroacupuncture stimulation (ES) to modulate body physiology at distant sites1–6 (for example, suppressing severe systemic inflammation6–9). Since the 1970s, an emerging organizational rule about these reflexes has been the presence of body-region specificity1–6. For example, ES at the hindlimb ST36 acupoin...
Article
Objective: Acupuncture, as an important part of Traditional Chinese Medicine, has been practiced for thousands of years in China and now all over the world, but the underlying neuroanatomical basis is still poorly understood. This article explores how acupuncture drives autonomic reflexes and why the widely used Streitberger sham-needling control s...
Article
The neuroanatomical basis behind acupuncture practice is still poorly understood. Here, we used intersectional genetic strategy to ablate NPY⁺ noradrenergic neurons and/or adrenal chromaffin cells. Using endotoxin-induced systemic inflammation as a model, we found that electroacupuncture stimulation (ES) drives sympathetic pathways in somatotopy- a...
Article
Full-text available
Animals and humans display two types of response to noxious stimuli. The first includes reflexive defensive responses that prevent or limit injury; a well-known example of these responses is the quick withdrawal of one’s hand upon touching a hot object. When the first-line response fails to prevent tissue damage (for example, a finger is burnt), th...
Article
The gate control theory proposes that Aβ mechanoreceptor inputs to spinal pain transmission T neurons are gated via feedforward inhibition, but it remains unclear how monosynaptic excitation is gated by disynaptic inhibitory inputs that arrive later. Here we report that Aβ-evoked, non-NMDAR-dependent EPSPs in T neurons are subthreshold, allowing ti...
Article
Full-text available
In 1905, Henry Head first suggested that transmission of pain-related protopathic information can be negatively modulated by inputs from afferents sensing innocuous touch and temperature. In 1965, Melzak and Wall proposed a more concrete gate control theory of pain that highlights the interaction between unmyelinated C fibers and myelinated A fiber...
Article
Full-text available
The somatic sensory neurons in dorsal root ganglia (DRG) detect and transmit a diverse array of sensory modalities, such as pain, itch, cold, warm, touch, and others. Recent genetic and single-cell RNA sequencing studies have revealed a group of DRG neurons that could be particularly relevant for acute and chronic itch information transmission. The...
Article
Full-text available
Mechanical hypersensitivity is a debilitating symptom for millions of chronic pain patients. It exists in distinct forms, including brush-evoked dynamic and filament-evoked punctate hypersensitivities. We reduced dynamic mechanical hypersensitivity induced by nerve injury or inflammation in mice by ablating a group of adult spinal neurons defined b...
Article
Full-text available
Light mechanical stimulation of hairy skin can induce a form of itch known as mechanical itch. This itch sensation is normally suppressed by inputs from mechanoreceptors; however, in many forms of chronic itch, including alloknesis, this gating mechanism is lost. Here we demonstrate that a population of spinal inhibitory interneurons that are defin...
Article
Full-text available
Mammalian skin is innervated by diverse, unmyelinated C fibers that are associated with senses of pain, itch, temperature, or touch. A key developmental question is how this neuronal cell diversity is generated during development. We reported previously that the runt domain transcription factor Runx1 is required to coordinate the development of the...
Data
Comparison of SNS-Cre/TdT vs Parv-Cre/TdT neuron expression profiles. Differential expression analysis of microarray data from SNS-Cre/TdTomato+ neurons (n = 4) vs Parv-Cre/TdTomato+ neurons (n = 4). Transcripts are ranked by fold-change, with the following information given: Affymetrix ID, genebank accession number, gene symbol, description, avera...
Data
Comparison of IB4 positive vs IB4 negative SNS-Cre/TdT neuron profiles. Differential expression analysis of microarray data from IB4+SNS-Cre/TdTomato+ neurons (n = 3) vs IB4−SNS-Cre/TdTomato+ neurons (n = 3). These cells were sorted from the same animals. Transcripts are ranked by fold-change, with the following information given: Affymetrix ID, ge...
Article
Full-text available
Pain information processing in the spinal cord has been postulated to rely on nociceptive transmission (T) neurons receiving inputs from nociceptors and Aβ mechanoreceptors, with Aβ inputs gated through feed-forward activation of spinal inhibitory neurons (INs). Here, we used intersectional genetic manipulations to identify these critical component...
Article
Full-text available
How the Merkel cell-neurite complex transduces and encodes touch remains unclear. Ikeda et al. now implicate Merkel cells as the primary sites of tactile transduction and the ion channel Piezo2 as the chief mechanotransducer. Surprisingly, Merkel cells also mediate allodynia, providing a new cellular target for chronic pain treatment.
Data
Full-text available
Pain information processing in the spinal cord has been postulated to rely on nociceptive transmission (T) neurons receiving inputs from nociceptors and Aβ mechanoreceptors, with Aβ inputs gated through feed-forward activation of spinal inhibitory neurons (INs). Here, we used intersectional genetic manipulations to identify these critical component...
Chapter
Somatic sensory neurons in the dorsal root ganglia (DRG) are composed of a variety of sensory modalities, such as pain-related nociceptors, itch-related pruriceptors, thermoreceptors and mechanoreceptors (Basbaum et al. 2009; Delmas et al. 2011). This chapter will focus on the neurotransmitter basis of somatic sensory information processing. Most,...
Article
Full-text available
Noxious stimuli usually cause pain and pain usually arises from noxious stimuli, but exceptions to these apparent truisms are the basis for clinically important problems and provide valuable insight into the neural code for pain. In this Review, we discuss how painful sensations arise. We argue that, although primary somatosensory afferents are tun...
Article
Full-text available
Mammalian pain-related sensory neurons are derived from TrkA lineage neurons located in the dorsal root ganglion. These neurons project to peripheral targets throughout the body, which can be divided into superficial and deep tissues. Here, we find that the transcription factor Runx1 is required for the development of many epidermis-projecting TrkA...
Article
Full-text available
Spatial and temporal cues govern the genesis of a diverse array of neurons located in the dorsal spinal cord, including dI1-dI6, dILA, and dILB subtypes, but their physiological functions are poorly understood. Here we generated a new line of conditional knock-out (CKO) mice, in which the homeobox gene Tlx3 was removed in dI5 and dILB cells. In the...
Article
Wnt proteins have been implicated in regulating a variety of developmental processes in the central nervous system (CNS). Secreted Frizzled-related protein 3 (sFRP3) is a member of the sFRP family that can inhibit the Wnt signaling by binding directly to Wnts via their regions of homology to the Wnt-binding domain of Frizzleds. Recent studies sugge...
Article
Full-text available
The peripheral terminals of primary sensory neurons detect histamine and non-histamine itch-provoking ligands through molecularly distinct transduction mechanisms. It remains unclear, however, whether these distinct pruritogens activate the same or different afferent fibers. Using a strategy of reversibly silencing specific subsets of murine prurit...
Article
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VGLUT3-expressing unmyelinated low-threshold mechanoreceptors (C-LTMRs) are proposed to mediate pleasant touch and/or pain, but the molecular programs controlling C-LTMR development are unknown. Here, we performed genetic fate mapping, showing that VGLUT3 lineage sensory neurons are divided into two groups, based on transient or persistent VGLUT3 e...
Article
Mammalian lung development consists of a series of precisely choreographed events that drive the progression from simple lung buds to the elaborately branched organ that fulfills the vital function of gas exchange. Strict transcriptional control is essential for lung development. Among the large number of transcription factors encoded in the mouse...
Article
Full-text available
Neurons in the mouse dorsal root ganglia (DRGs) are composed of a variety of sensory modalities, such as pain-related nociceptors, itch-related pruriceptors, and thermoceptors. All these neurons are derived from late-born neurons that are initially marked by the expression of the nerve growth factor receptor TrkA. During perinatal and postnatal dev...
Article
Full-text available
Itch, also known as pruritus, is a common, intractable symptom of several skin diseases, such as atopic dermatitis and xerosis. TLRs mediate innate immunity and regulate neuropathic pain, but their roles in pruritus are elusive. Here, we report that scratching behaviors induced by histamine-dependent and -independent pruritogens are markedly reduce...
Article
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Lengthy developmental programs generate cell diversity within an organotypic framework, enabling the later physiological actions of each organ system. Cell identity, cell diversity and cell function are determined by cell type-specific transcriptional programs; consequently, transcriptional regulatory factors are useful markers of emerging cellular...
Article
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The somatic sensory system includes a variety of sensory modalities, such as touch, pain, itch, and temperature sensitivity. The coding of these modalities appears to be best explained by the population-coding theory, which is composed of the following features. First, an individual somatic sensory afferent is connected with a specific neural circu...
Article
Full-text available
The neurocircuits that process somatic sensory information in the dorsal horn of the spinal cord are still poorly understood, with one reason being the lack of Cre lines for genetically marking or manipulating selective subpopulations of dorsal horn neurons. Here we describe Tac2-Cre mice that were generated to express the Cre recombinase gene from...
Article
Full-text available
In adult mammals, the phenotype of half of all pain-sensing (nociceptive) sensory neurons is tonically modulated by growth factors in the glial cell line-derived neurotrophic factor (GDNF) family that includes GDNF, artemin (ARTN) and neurturin (NRTN). Each family member binds a distinct GFRα family co-receptor, such that GDNF, NRTN and ARTN bind G...
Article
Itch can be suppressed by painful stimuli, but the underlying neural basis is unknown. We generated conditional null mice in which vesicular glutamate transporter type 2 (VGLUT2)-dependent synaptic glutamate release from mainly Nav1.8-expressing nociceptors was abolished. These mice showed deficits in pain behaviors, including mechanical pain, heat...
Article
Full-text available
The somatic sensory system responds to stimuli of distinct modalities, including touch, pain, itch, and temperature sensitivity. In the past century, great progress has been made in understanding the coding of these sensory modalities. From this work, two major features have emerged. First, there are specific neuronal circuits or labeled lines tran...
Article
Neurons in the dorsal root ganglia (DRG) are composed of a variety of sensory modalities, three of which are pain-sensing nociceptors, temperature-sensing thermoceptors, and itch-sensing pruriceptors. All these neurons are emerged from a common pool of embryonic DRG neurons that are marked by the expression of the neurotrophin receptor TrkA. Here w...
Data
Runx1 was required for Mrgprb5, GluR5, PKCq, and TRPA1 expression, and for the maintenance of Mrgprd expression. (A) In situ hybridization using the indicated probe on lumbar L4/5 DRG from P30 Runx1F/F control mice and Runx1F/F;WntCre early knockout mice. (B) Graph shows RT-PCR measuring mRNA levels of TRPA1 using adult L4-5 DRG from Runx1F/F contr...
Data
Double labeling of GFP protein (green) and indicated RNA probe (red) in lumbar DRG from P30 MrgprdΔEGFP animals. Mrgprd was used here as a surrogate marker for Runx1+ neurons; see main text for details. Note that Mrgprb5, GluR5, TRPC3, and PKCq were largely overlapping with GFP and were thus predominantly in Runx1-persistent neurons. Quantitative d...
Data
Generation of Runx1F/F;Nav1.8Cre late conditional knockout (L-CKO) in the DRG. (A) Schematic showing the conditional Runx1 allele. Exon 4, encoding part of the DNA binding Runt domain, was flanked by two loxP sequences (black triangles). Deletion of this exon generated a null allele. The neo cassette was also flanked by loxP sites. After crossing R...
Data
Afferent central innervation of IB4+ sensory fibers in the dorsal horn was impaired in Runx1F/F;Nav1.8Cre late knockout. Double staining of IB4 (green) and CGRP (red) on P30 dorsal horn sections of control Runx1F/F and Runx1F/F;Nav1.8Cre mice. In control mice, peptidergic CGRP+ fibers innervated the superficial lamina, while nonpeptidergic IB4+ fib...
Data
Generation of Tau-Runx1F;Nav1.8Cre mice that drove constitutive Runx1 expression in most nociceptors. (A) Schematic showing the conditional knock-in of the Tau-Runx1 allele. A lox-STOP-lox-Runx1-IRES-nlsLacZ-neo cassette was inserted into exon 2 (black box) of the Tau locus. After crossing Tau-Runx1F mice with Nav1.8Cre mice, The 'STOP' was excised...
Data
Expression of Ret, TrkA, CGRP and DRASIC in Runx1F/F;Nav1.8Cre late knockout mice. (A) In situ hybridization with a Ret probe on transverse sections through adult lumbar DRG of control Runx1F/F mice and mutant Runx1F/F;Nav1.8Cre mice. To the right of the panels, a graph showed that the average (± SEM) number of neurons expressing Ret per set of lum...
Data
Double Staining of CGRP with Mrgprc11 and with Runx1. (A) A majority of Mrgprc11+ neurons were peptidergic. Double staining of CGRP protein (red) and Mrgprc11 mRNA (green) on sections from P30 lumbar DRG from WT mice. Note that 71% of total Mrgprc11+ neurons (67 of 94) coexpressed CGRP (arrows). (B) Runx1 was expressed in a small subset of peptider...
Data
Development of proprioceptors and mechanoceptors was unaffected in Tau-Runx1F;Nav1.8Cre mice. (A) In situ hybridization using the indicated probes on sections through adult lumbar (L4/L5) DRG of Tau-Runx1F control and Tau-Runx1F;Nav1.8Cre mutant mice. (B) Graph showing the average (± SEM) of the total number of neurons expressing the indicated prob...
Data
Examination of afferent central innervation in the dorsal horn of Tau-Runx1F;Nav1.8Cre mutants. Double staining of IB4 (green) and CGRP (red) on P30 dorsal horn sections of Tau-Runx1F control and Tau-Runx1F;Nav1.8Cre mutant mice. Note that the residual CGRP+ fibers still innervated the superficial lamina, and IB4+ fibers also showed normal innervat...
Article
Full-text available
The cellular and molecular programs that control specific types of pain are poorly understood. We reported previously that the runt domain transcription factor Runx1 is initially expressed in most nociceptors and controls sensory neuron phenotypes necessary for inflammatory and neuropathic pain. Here we show that expression of Runx1-dependent ion c...
Article
Itch is the least well understood of all the somatic senses, and the neural circuits that underlie this sensation are poorly defined. Here we show that the atonal-related transcription factor Bhlhb5 is transiently expressed in the dorsal horn of the developing spinal cord and appears to play a role in the formation and regulation of pruritic (itch)...
Article
The rapidly adapting (RA) low-threshold mechanoreceptors respond to movement of the skin and vibration and are critical for the perception of texture and shape. In this issue of Neuron, two papers (Bourane et al. and Luo et al.) demonstrate that early-born Ret+ sensory neurons are RA mechanoreceptors, whose peripheral nerve terminals are associated...
Article
Full-text available
Forward genetic screens in genetically accessible invertebrate organisms such as Drosophila melanogaster have shed light on transcription factors that specify formation of neurons in the vertebrate CNS. However, invertebrate models have, to date, been uninformative with respect to genes that specify formation of the vertebrate glial lineages. All r...
Article
Full-text available
Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor alpha (TNF-alpha) transiently activated JNK via TNF receptor-1. Cytokine array indicated...
Article
Runt-related (RUNX) transcription factors are evolutionarily conserved regulators of a number of developmental mechanisms. RUNX proteins often control the balance between proliferation and differentiation and alterations of their functions are associated with different types of cancer and other human pathologies. Moreover, RUNX factors control impo...
Article
Whether the brain tumor medulloblastoma originates from stem cells or restricted progenitor cells is unclear. To investigate this, we activated oncogenic Hedgehog (Hh) signaling in multipotent and lineage-restricted central nervous system (CNS) progenitors. We observed that normal unipotent cerebellar granule neuron precursors (CGNPs) derive from h...
Article
Full-text available
The dorsal spinal cord synthesizes a variety of neuropeptides that modulate the transmission of nociceptive sensory information. Here, we used genetic fate mapping to show that Tlx3(+) spinal cord neurons and their derivatives represent a heterogeneous population of neurons, marked by partially overlapping expression of a set of neuropeptide genes,...
Article
Full-text available
The mechanisms by which proneural basic helix-loop-helix (bHLH) factors control neurogenesis have been characterized, but it is not known how they specify neuronal cell-type identity. Here, we provide evidence that two conserved serine residues on the bHLH factor neurogenin 2 (Ngn2), S231 and S234, are phosphorylated during motor neuron differentia...
Article
Full-text available
Mrg class G-protein-coupled receptors (GPCRs) are expressed exclusively in sensory neurons in the trigeminal and dorsal root ganglia. Pharmacological activation of Mrg proteins is capable of modulating sensory neuron activities and elicits nociceptive effects. In this study, we illustrate a control mechanism that allows the Runx1 runt domain transc...
Article
In order to deal effectively with danger, it is imperative to know about it. This is what nociceptors do--these primary sensory neurons are specialized to detect intense stimuli and represent, therefore, the first line of defense against any potentially threatening or damaging environmental inputs. By sensing noxious stimuli and contributing to the...
Article
Disorders of cerebellar development can result in neurological disease and cancer. The identity of transcription factors that may uniquely mark and/or regulate development of single cerebellar cell types, however, is poorly understood. We used a library of approximately 1100 probes for expression of transcription factor (TF)-encoding genes (>70% of...
Article
Transcription factors (TFs) play pivotal roles in directing the formation of neurons and glia. Here I will review the recent genome-scale analysis of the expression of TFs in the developing mouse nervous system and discuss the logic by which TFs control the establishment of neuronal phenotype. Accumulating evidence suggests that while combinatorial...
Article
Sensory information from the periphery is integrated and transduced by excitatory and inhibitory interneurons in the dorsal spinal cord. Recent studies have identified a number of postmitotic factors that control the generation of these sensory interneurons. We show that Gsh1/2 and Ascl1 (Mash1), which are expressed in sensory interneuron progenito...
Chapter
Glutamatergic and GABAergic are two principal excitatory and inhibitory neurons, respectively, in the vertebrate nervous system. Recent studies have gained significant insights into the mechanisms by which neurons make the choice between these two fundamental neuronal cell fates. First, region-specific transcription factors such as the Tlx class ho...
Article
In mammals, the perception of pain is initiated by the transduction of noxious stimuli through specialized ion channels and receptors expressed by nociceptive sensory neurons. The molecular mechanisms responsible for the specification of distinct sensory modality are, however, largely unknown. We show here that Runx1, a Runt domain transcription fa...
Article
Full-text available
Most neurons in vertebrates make a developmental choice between two principal neurotransmitter phenotypes (glutamatergic versus GABAergic). Here we show that the homeobox gene Lbx1 determines a GABAergic cell fate in the dorsal spinal cord at early embryonic stages. In Lbx1-/- mice, the presumptive GABAergic neurons are transformed into glutamaterg...
Article
Full-text available
In the developing brain, transcription factors (TFs) direct the formation of a diverse array of neurons and glia. We identifed 1445 putative TFs in the mouse genome. We used in situ hybridization to map the expression of over 1000 of these TFs and TF-coregulator genes in the brains of developing mice. We found that 349 of these genes showed restric...
Article
Full-text available
Glutamatergic and GABAergic neurons mediate much of the excitatory and inhibitory neurotransmission, respectively, in the vertebrate nervous system. The process by which developing neurons select between these two cell fates is poorly understood. Here we show that the homeobox genes Tlx3 and Tlx1 determine excitatory over inhibitory cell fates in t...
Article
Full-text available
Serotonergic (5-HT) neurons in the brainstem modulate a wide range of physiological processes and behaviors. Two transcription factor genes, Pet-1 and Nkx2.2, are necessary but not sufficient to specify the 5-HT transmitter phenotype. Here we show that the Lim class homeobox gene Lmx1b is required for proper formation of the entire 5-HT system in t...