Wt1 positive neurons in the hindbrain are essential for respiration

AbstractNeuronal networks commonly referred to as central pattern generator (CPG) networks coordinate the generation of rhythmic activity like locomotion and respiration. These networks are proposed to exhibit a high degree of homology in their development. Their establishment is influenced by a variety of transcription factors. One of them is the Wilms tumor protein Wt1 that is present in dI6 neurons of the ventral spinal cord, which are involved in the coordination of locomotion. Here we report about the so far undescribed presence of Wt1 in neurons of the caudoventral medulla oblongata and their impact on respiration. By performing marker analyses, we were able to characterize these Wt1 positive (+) cells as dB4 neurons. The temporal pattern of Wt1 occurrence suggests a role for Wt1 in the differentiation of dB4 neurons during embryonic and postnatal development. Conditional knockout of Wt1 in these cells caused an altered population size of V0 neurons already in the developing hindbrain leading to a decline in the respiration rate in the adults. Thereby, we confirmed and extended the so far proposed homology between neurons of the dB4 domain in the hindbrain and dI6 neurons of the spinal cord in terms of development and function. Ablation of Wt1+ dB4 neurons resulted in the death of neonates due to the inability to initiate respiration suggesting a vital role for Wt1+ dB4 neurons in breathing. These results extend the role of Wt1 in the CNS and show that in addition to its function in differentiation of dI6 neurons it also contributes to the development of dB4 neurons in the hindbrain that are critically involved in the regulation of respiration.

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Wt1 Positive dB4 Neurons in the Hindbrain Are Crucial for Respiration

Frontiers in Neuroscience ◽

10.3389/fnins.2020.529487 ◽

2020 ◽

Vol 14 ◽

Author(s):

Danny Schnerwitzki ◽

Christian Hayn ◽

Birgit Perner ◽

Christoph Englert

Keyword(s):

Spinal Cord ◽

Wilms Tumor ◽

Rhythmic Activity ◽

Pattern Generator ◽

Vital Role ◽

Conditional Knockout ◽

Regulation Of Respiration ◽

Temporal Occurrence ◽

And Function

Central pattern generator (CPG) networks coordinate the generation of rhythmic activity such as locomotion and respiration. Their development is driven by various transcription factors, one of which is the Wilms tumor protein (Wt1). It is present in dI6 neurons of the mouse spinal cord, and involved in the coordination of locomotion. Here we report about the presence of Wt1 in neurons of the caudoventral medulla oblongata and their impact on respiration. By employing immunohistofluorescence staining, we were able to characterize these Wt1 positive (+) cells as dB4 neurons. The temporal occurrence of Wt1 suggests a role for this transcription factor in the differentiation of dB4 neurons during embryonic and postnatal development. Conditional knockout of Wt1 in these cells caused an altered population size of V0 neurons already in the developing hindbrain, leading to a decline in the respiration rate in the adults. Thereby, we confirmed and extended the previously proposed similarity between dB4 neurons in the hindbrain and dI6 neurons of the spinal cord, in terms of development and function. Ablation of Wt1+ dB4 neurons resulted in the death of neonates due to the inability to initiate respiration, suggesting a vital role for Wt1+ dB4 neurons in breathing. These results expand the role of Wt1 in the CNS and show that, in addition to its function in differentiation of dI6 neurons, it also contributes to the development of dB4 neurons in the hindbrain that are critically involved in the regulation of respiration.

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The enigmatic ribosomal stalk

Quarterly Reviews of Biophysics ◽

10.1017/s0033583518000100 ◽

2018 ◽

Vol 51 ◽

Cited By ~ 11

Author(s):

Anders Liljas ◽

Suparna Sanyal

Keyword(s):

Early Phase ◽

Ribosomal Subunit ◽

Structure And Function ◽

Large Ribosomal Subunit ◽

Translation Factors ◽

Ribosomal Stalk ◽

And Function ◽

High Degree

Abstract The large ribosomal subunit has a distinct feature, the stalk, extending outside the ribosome. In bacteria it is called the L12 stalk. The base of the stalk is protein uL10 to which two or three dimers of proteins bL12 bind. In archea and eukarya P1 and P2 proteins constitute the stalk. All these extending proteins, that have a high degree of flexibility due to a hinge between their N- and C-terminal parts, are essential for proper functionalization of some of the translation factors. The role of the stalk proteins has remained enigmatic for decades but is gradually approaching an understanding. In this review we summarise the knowhow about the structure and function of the ribosomal stalk till date starting from the early phase of ribosome research.

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The Role of Mcl-1 in Embryonic Neural Precursor Cell Apoptosis

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.659531 ◽

2021 ◽

Vol 9 ◽

Author(s):

Robert T. Flemmer ◽

Sarah P. Connolly ◽

Brittany A. Geizer ◽

Joseph T. Opferman ◽

Jacqueline L. Vanderluit

Keyword(s):

Spinal Cord ◽

Nervous System ◽

Precursor Cell ◽

Embryonic Lethality ◽

Conditional Knockout ◽

Neural Precursor ◽

Null Mouse ◽

Neural Precursor Cell ◽

Thoracic Spinal Cord

Myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic Bcl-2 protein, regulates neural precursor cell (NPC) survival in both the developing and adult mammalian nervous system. It is unclear when during the neurogenic period Mcl-1 becomes necessary for NPC survival and whether Bax is the sole pro-apoptotic target of Mcl-1. To address these questions, we used the nervous system-specific Nestin-Cre Mcl-1 conditional knockout mouse line (Mcl-1 CKO) to assess the anti-apoptotic role of Mcl-1 in developmental neurogenesis. Loss of Mcl-1 resulted in a wave of apoptosis beginning in the brainstem and cervical spinal cord at embryonic day 9.5 (E9.5) and in the forebrain at E10.5. Apoptosis was first observed ventrally in each region and spread dorsally over time. Within the spinal cord, apoptosis also spread in a rostral to caudal direction following the path of differentiation. Breeding the Mcl-1 CKO mouse with the Bax null mouse rescued the majority of NPC from apoptosis except in the dorsomedial brainstem and ventral thoracic spinal cord where only 50% were rescued. This demonstrates that Mcl-1 promotes NPC survival primarily by inhibiting the activation of Bax, but that Bax is not the sole pro-apoptotic target of Mcl-1 during embryonic neurogenesis. Interestingly, although co-deletion of Bax rescued the majority of NPC apoptosis, it resulted in embryonic lethality at E13, whereas conditional deletion of both Mcl-1 and Bax rescued embryonic lethality. In summary, this study demonstrates the widespread dependency on Mcl-1 during nervous system development.

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Diminished ventral oligodendrocyte precursor generation results in the subsequent over-production of dorsal oligodendrocyte precursors of aberrant morphology and function

10.1101/2020.03.09.983908 ◽

2020 ◽

Author(s):

Lev Starikov ◽

Andreas H. Kottmann

Keyword(s):

Spinal Cord ◽

Motor Neurons ◽

Ventricular Zone ◽

Normal Numbers ◽

Spinal Cord Development ◽

Oligodendrocyte Precursor ◽

And Function ◽

Sod1 Mouse ◽

Lateral Sclerosis ◽

Ventral Spinal Cord

AbstractOligodendrocyte precursor cells (OPCs) arise sequentially first from a ventral and then from a dorsal precursor domain at the end of neurogenesis during spinal cord development. Whether the sequential production of OPCs is of physiological significance has not been examined. Here we show that ablating Shh signaling from nascent ventricular zone derivatives and partially from the floor plate results in a severe diminishment of ventral derived OPCs but normal numbers of motor neurons in the postnatal spinal cord. In the absence of ventral vOPCs, dorsal dOPCs populate the entire spinal cord resulting in an increased OPC density in the ventral horns. These OPCs take on an altered morphology, do not participate in the removal of excitatory vGlut1 synapses from injured motor neurons, and exhibit morphological features similar to those found in the vicinity of motor neurons in the SOD1 mouse model of Amyotrophic Lateral Sclerosis (ALS). Our data indicates that vOPCs prevent dOPCs from invading ventral spinal cord laminae and suggests that vOPCs have a unique ability to communicate with injured motor neurons.

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Autonomous TNF is critical for in vivo monocyte survival in steady state and inflammation

Journal of Experimental Medicine ◽

10.1084/jem.20160499 ◽

2017 ◽

Vol 214 (4) ◽

pp. 905-917 ◽

Cited By ~ 35

Author(s):

Yochai Wolf ◽

Anat Shemer ◽

Michal Polonsky ◽

Mor Gross ◽

Alexander Mildner ◽

...

Keyword(s):

Spinal Cord ◽

Mononuclear Phagocytes ◽

Autoimmune Encephalomyelitis ◽

Wild Type Counterpart ◽

And Function ◽

Necrosis Factor ◽

Experimental Autoimmune

Monocytes are circulating mononuclear phagocytes, poised to extravasate to sites of inflammation and differentiate into monocyte-derived macrophages and dendritic cells. Tumor necrosis factor (TNF) and its receptors are up-regulated during monopoiesis and expressed by circulating monocytes, as well as effector monocytes infiltrating certain sites of inflammation, such as the spinal cord, during experimental autoimmune encephalomyelitis (EAE). In this study, using competitive in vitro and in vivo assays, we show that monocytes deficient for TNF or TNF receptors are outcompeted by their wild-type counterpart. Moreover, monocyte-autonomous TNF is critical for the function of these cells, as TNF ablation in monocytes/macrophages, but not in microglia, delayed the onset of EAE in challenged animals and was associated with reduced acute spinal cord infiltration of Ly6Chi effector monocytes. Collectively, our data reveal a previously unappreciated critical cell-autonomous role of TNF on monocytes for their survival, maintenance, and function.

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The critical role of Krüppel-like factors in kidney disease

AJP Renal Physiology ◽

10.1152/ajprenal.00550.2016 ◽

2017 ◽

Vol 312 (2) ◽

pp. F259-F265 ◽

Cited By ~ 17

Author(s):

Sandeep K. Mallipattu ◽

Chelsea C. Estrada ◽

John C. He

Keyword(s):

Current Knowledge ◽

Critical Role ◽

Vital Role ◽

Glomerular Filtration Barrier ◽

Kidney Fibrosis ◽

Physiological Processes ◽

Filtration Barrier ◽

And Function ◽

Mammalian Embryonic Development

Krüppel-like factors (KLFs) are a family of zinc-finger transcription factors critical to mammalian embryonic development, regeneration, and human disease. There is emerging evidence that KLFs play a vital role in key physiological processes in the kidney, ranging from maintenance of glomerular filtration barrier to tubulointerstitial inflammation to progression of kidney fibrosis. Seventeen members of the KLF family have been identified, and several have been well characterized in the kidney. Although they may share some overlap in their downstream targets, their structure and function remain distinct. This review highlights our current knowledge of KLFs in the kidney, which includes their pattern of expression and their function in regulating key biological processes. We will also critically examine the currently available literature on KLFs in the kidney and offer some key areas in need of further investigation.

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Identification of a Sulf2-dependant astrocyte subtype that stands out through the expression of Olig2 in the ventral spinal cord

10.1101/430074 ◽

2018 ◽

Author(s):

David Ohayon ◽

Nathalie Escalas ◽

Philippe Cochard ◽

Bruno Glise ◽

Cathy Danesin ◽

...

Keyword(s):

Spinal Cord ◽

Extracellular Enzyme ◽

Oligodendrocyte Precursor Cells ◽

Spinal Cord Development ◽

Cell Diversity ◽

Oligodendrocyte Precursor ◽

Editing Enzyme ◽

Ventral Spinal Cord ◽

Developing Spinal Cord

SummaryDuring spinal cord development, both spatial and temporal mechanisms operate to generate glial cell diversity. Here, we addressed the role of the Heparan Sulfate-editing enzyme Sulf2 in the control of gliogenesis in the mouse developing spinal cord and found an unanticipated function for this enzyme. Sulf2 is expressed in ventral spinal progenitors at initiation of gliogenesis, including in Olig2-expressing cells of the pMN domain known to generate most spinal cord oligodendrocyte precursor cells (OPCs). We found that Sulf2 is dispensable for OPC development but required for proper generation of an as-yet-unidentified astrocyte precursor cell (AP) subtype. These cells, like OPCs, express Olig2 while populating the spinal parenchyma at embryonic stages but also retain Olig2 expression as they differentiate into mature astrocytes. We therefore identify a spinal Olig2-expressing AP subtype that segregates early under the influence of the extracellular enzyme Sulf2.

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Role of Macrophages and Microglia in Zebrafish Regeneration

International Journal of Molecular Sciences ◽

10.3390/ijms21134768 ◽

2020 ◽

Vol 21 (13) ◽

pp. 4768 ◽

Cited By ~ 4

Author(s):

Susanna R. Var ◽

Christine A. Byrd-Jacobs

Keyword(s):

Nervous System ◽

Immune Cells ◽

Immune Cell ◽

Innate Immune ◽

Inflammatory Processes ◽

The Central Nervous System ◽

And Function ◽

High Degree ◽

Human Nerve

Currently, there is no treatment for recovery of human nerve function after damage to the central nervous system (CNS), and there are limited regenerative capabilities in the peripheral nervous system. Since fish are known for their regenerative abilities, understanding how these species modulate inflammatory processes following injury has potential translational importance for recovery from damage and disease. Many diseases and injuries involve the activation of innate immune cells to clear damaged cells. The resident immune cells of the CNS are microglia, the primary cells that respond to infection and injury, and their peripheral counterparts, macrophages. These cells serve as key modulators of development and plasticity and have been shown to be important in the repair and regeneration of structure and function after injury. Zebrafish are an emerging model for studying macrophages in regeneration after injury and microglia in neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease. These fish possess a high degree of neuroanatomical, neurochemical, and emotional/social behavioral resemblance with humans, serving as an ideal simulator for many pathologies. This review explores literature on macrophage and microglial involvement in facilitating regeneration. Understanding innate immune cell behavior following damage may help to develop novel methods for treating toxic and chronic inflammatory processes that are seen in trauma and disease.

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Sirtuins, Bioageing, and Cancer

Journal of Aging Research ◽

10.4061/2011/235754 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 20

Author(s):

D. McGuinness ◽

D. H. McGuinness ◽

J. A. McCaul ◽

P. G. Shiels

Keyword(s):

Cell Cycle ◽

Genomic Stability ◽

Degenerative Diseases ◽

Critical Junctures ◽

Age Related ◽

Wide Range ◽

Telomere Function ◽

And Function ◽

High Degree

The Sirtuins are a family of orthologues of yeast Sir2 found in a wide range of organisms from bacteria to man. They display a high degree of conservation between species, in both sequence and function, indicative of their key biochemical roles. Sirtuins are heavily implicated in cell cycle, cell division, transcription regulation, and metabolism, which places the various family members at critical junctures in cellular metabolism. Typically, Sirtuins have been implicated in the preservation of genomic stability and in the prolongation of lifespan though many of their target interactions remain unknown. Sirtuins play key roles in tumourigenesis, as some have tumour-suppressor functions and others influence tumours through their control of the metabolic state of the cell. Their links to ageing have also highlighted involvement in various age-related and degenerative diseases. Here, we discuss the current understanding of the role of Sirtuins in age-related diseases while taking a closer look at their roles and functions in maintaining genomic stability and their influence on telomerase and telomere function.

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Housekeeping in the Hydrosphere: Microbial Cooking, Cleaning, and Control under Stress

Life ◽

10.3390/life11020152 ◽

2021 ◽

Vol 11 (2) ◽

pp. 152

Author(s):

Bopaiah Biddanda ◽

Deborah Dila ◽

Anthony Weinke ◽

Jasmine Mancuso ◽

Manuel Villar-Argaiz ◽

...

Keyword(s):

Organic Matter ◽

Remote Control ◽

Bacterial Biomass ◽

Vital Role ◽

Ecosystem Structure ◽

Heterotrophic Microbes ◽

And Function ◽

And Control ◽

Ecosystem Structure And Function

Who’s cooking, who’s cleaning, and who’s got the remote control within the waters blanketing Earth? Anatomically tiny, numerically dominant microbes are the crucial “homemakers” of the watery household. Phytoplankton’s culinary abilities enable them to create food by absorbing sunlight to fix carbon and release oxygen, making microbial autotrophs top-chefs in the aquatic kitchen. However, they are not the only bioengineers that balance this complex household. Ubiquitous heterotrophic microbes including prokaryotic bacteria and archaea (both “bacteria” henceforth), eukaryotic protists, and viruses, recycle organic matter and make inorganic nutrients available to primary producers. Grazing protists compete with viruses for bacterial biomass, whereas mixotrophic protists produce new organic matter as well as consume microbial biomass. When viruses press remote-control buttons, by modifying host genomes or lysing them, the outcome can reverberate throughout the microbial community and beyond. Despite recognition of the vital role of microbes in biosphere housekeeping, impacts of anthropogenic stressors and climate change on their biodiversity, evolution, and ecological function remain poorly understood. How trillions of the smallest organisms in Earth’s largest ecosystem respond will be hugely consequential. By making the study of ecology personal, the “housekeeping” perspective can provide better insights into changing ecosystem structure and function at all scales.

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