ABSTRACT
Satellite glia are the major glial cells in sympathetic ganglia, enveloping neuronal cell bodies. Despite this intimate association, the extent to which sympathetic functions are influenced by satellite glia in vivo remains unclear. Here, we show that satellite glia are critical for metabolism, survival, and activity of sympathetic neurons and modulate autonomic behaviors in mice. Adult ablation of satellite glia results in impaired mTOR signaling, soma atrophy, reduced noradrenergic enzymes, and loss of sympathetic neurons. However, persisting neurons have elevated activity, and satellite glia-ablated mice show increased pupil dilation and heart rate, indicative of enhanced sympathetic tone. Satellite glia-specific deletion of Kir4.1, an inward-rectifying potassium channel, largely recapitulates the cellular defects observed in glia-ablated mice, suggesting that satellite glia act in part via K+-dependent mechanisms. These findings highlight neuron-satellite glia as functional units in regulating sympathetic output, with implications for disorders linked to sympathetic hyper-activity such as cardiovascular disease and hypertension.
Subject(s)
Ganglia, Sympathetic , Neuroglia , Animals , Cell Survival , Mice , Neuroglia/physiology , Neurons , Signal TransductionABSTRACT
Satellite glia are the major glial type found in sympathetic and sensory ganglia in the peripheral nervous system, and specifically, contact neuronal cell bodies. Sympathetic and sensory neurons differ in morphological, molecular, and electrophysiological properties. However, the molecular diversity of the associated satellite glial cells remains unclear. Here, using single-cell RNA sequencing analysis, we identify five different populations of satellite glia from sympathetic and sensory ganglia. We define three shared populations of satellite glia enriched in immune-response genes, immediate-early genes, and ion channels/ECM-interactors, respectively. Sensory- and sympathetic-specific satellite glia are differentially enriched for modulators of lipid synthesis and metabolism. Sensory glia are also specifically enriched for genes involved in glutamate turnover. Furthermore, satellite glia and Schwann cells can be distinguished by unique transcriptional signatures. This study reveals the remarkable heterogeneity of satellite glia in the peripheral nervous system.
Subject(s)
Ganglia, Sensory/metabolism , Ganglia, Spinal/metabolism , Neuroglia/metabolism , Schwann Cells/metabolism , Animals , Ganglia, Sympathetic/metabolism , Humans , Mice , Neurons/metabolism , Neurons, Afferent , Peripheral Nervous System/metabolismABSTRACT
Tissue homeostasis requires somatic stem cell maintenance; however, mechanisms regulating this process during organogenesis are not well understood. Here, we identify asymmetrically renewing basal and luminal stem cells in the mammary end bud. We demonstrate that SLIT2/ROBO1 signaling regulates the choice between self-renewing asymmetric cell divisions (ACDs) and expansive symmetric cell divisions (SCDs) by governing Inscuteable (mInsc), a key member of the spindle orientation machinery, through the transcription factor Snail (SNAI1). Loss of SLIT2/ROBO1 signaling increases SNAI1 in the nucleus. Overexpression of SNAI1 increases mInsc expression, an effect that is inhibited by SLIT2 treatment. Increased mInsc does not change cell proliferation in the mammary gland (MG) but instead causes more basal cap cells to divide via SCD, at the expense of ACD, leading to more stem cells and larger outgrowths. Together, our studies provide insight into how the number of mammary stem cells is regulated by the extracellular cue SLIT2.
Subject(s)
Cell Cycle Proteins/metabolism , Cell Self Renewal , Intercellular Signaling Peptides and Proteins/metabolism , Mammary Glands, Human/cytology , Nerve Tissue Proteins/metabolism , Receptors, Immunologic/metabolism , Stem Cells/metabolism , Transcription Factors/metabolism , Animals , Asymmetric Cell Division , Cell Cycle Proteins/genetics , Cell Line, Tumor , Humans , Intercellular Signaling Peptides and Proteins/genetics , Mammary Glands, Human/growth & development , Mice , Mice, Inbred C57BL , Nerve Tissue Proteins/genetics , Receptors, Immunologic/genetics , Signal Transduction , Snail Family Transcription Factors , Stem Cells/cytology , Stem Cells/physiology , Transcription Factors/genetics , Roundabout ProteinsABSTRACT
Traditionally, geckos have been conceived to exhibit paedomorphic features relative to other lizards (e.g., large eyes, less extensively ossified skulls, and amphicoelous and notochordal vertebrae). In contrast, peramorphosis has not been considered an important process in shaping their morphology. Here, we studied different sized specimens of Gekko gecko to document ontogenetic changes in cranial anatomy, especially near maturity. Comparison of this species with available descriptions of other geckos resulted in the identification of 14 cranial characteristics that are expressed more strongly with size increase. These characteristics become move evident in later stages of post-hatching development, especially near maturation, and are, therefore, attributed to peramorphosis (hyperossification). ACCTRAN and DELTRAN character optimizations were applied to these characters using a tree of 11 genera derived from a gekkotan molecular phylogeny. This analysis revealed that G. gecko expresses the majority of these putative peramorphic features near maturity, and that some of these features are also expressed in species closely related to G. gecko. The characters studied have the potential to be applied in future phylogenetic and taxonomic studies of this group of lizards.
