Expression Analyses of Mediator Complex Subunit 13-Like: A Responsible Gene for Neurodevelopmental Disorders during Mouse Brain Development

2021 ◽  
pp. 1-10
Author(s):  
Nanako Hamada ◽  
Ikuko Iwamoto ◽  
Masashi Nishikawa ◽  
Koh-ichi Nagata
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Brain Development ◽  
Developmental Stage ◽  
Expression Profile ◽  
Neurodevelopmental Disorders ◽  
Mediator Complex ◽  
Cortical Plate ◽  
The Central Nervous System

MED13L (mediator complex subunit 13-like) is a component of the mediator complex, which functions as a regulator for gene transcription. Since gene abnormalities in MED13L are responsible for neurodevelopmental disorders, MED13L is presumed to play an essential role in brain development. In this study, we prepared a specific antibody against MED13L, anti-MED13L, and analyzed its expression profile in mouse tissues with focusing on the central nervous system. In Western blotting, MED13L exhibited a tissue-dependent expression profile in the adult mouse and was expressed in a developmental stage-dependent manner in brain. In immunofluorescence analyses, MED13L was at least partially colocalized with pre- and post-synaptic markers, synaptophysin, and PSD95, in primary cultured hippocampal neurons. Immunohistochemical analyses revealed that MED13L was relatively highly expressed in ventricular zone surface of cerebral cortex, and was also located both in the cytoplasm and nucleus of neurons in the cortical plate at embryonic day 14. Then, MED13L showed diffuse cytoplasmic distribution throughout the cerebral cortex at the postnatal day (P) 30. In addition, MED13L appeared to be localized in cell type- and developmental stage-specific manners in the hippocampus and cerebellum. These results suggest that MED13L is involved in the development of the central nervous system and synaptic function.

scholarly journals Impaired αVβ8 and TGFβ signaling lead to microglial dysmaturation and neuromotor dysfunction

2019 ◽  
Vol 216 (4) ◽  
pp. 900-915 ◽  
Author(s):  
Thomas D. Arnold ◽  
Carlos O. Lizama ◽  
Kelly M. Cautivo ◽  
Nicolas Santander ◽  
Lucia Lin ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Neurodevelopmental Disorders ◽  
Tgfβ Signaling ◽  
Critical Determinant ◽  
Conditional Deletion ◽  
Stepwise Development ◽  
The Central Nervous System

Microglia play a pivotal role in the coordination of brain development and have emerged as a critical determinant in the progression of neurodegenerative diseases; however, the role of microglia in the onset and progression of neurodevelopmental disorders is less clear. Here we show that conditional deletion of αVβ8 from the central nervous system (Itgb8ΔCNS mice) blocks microglia in their normal stepwise development from immature precursors to mature microglia. These “dysmature” microglia appear to result from reduced TGFβ signaling during a critical perinatal window, are distinct from microglia with induced reduction in TGFβ signaling during adulthood, and directly cause a unique neurodevelopmental syndrome characterized by oligodendrocyte maturational arrest, interneuron loss, and spastic neuromotor dysfunction. Consistent with this, early (but not late) microglia depletion completely reverses this phenotype. Together, these data identify novel roles for αVβ8 and TGFβ signaling in coordinating microgliogenesis with brain development and implicate abnormally programmed microglia or their products in human neurodevelopmental disorders that share this neuropathology.

scholarly journals Microglia-mediated synaptic elimination in neuronal development and disease

2018 ◽  
Vol 119 (1) ◽  
pp. 1-4 ◽  
Author(s):  
Brendan S. Whitelaw
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Immune Cells ◽  
Neurodevelopmental Disorders ◽  
Neuronal Development ◽  
Neuronal Connectivity ◽  
Wide Range ◽  
The Central Nervous System

It has recently become clear that microglia, the immune cells of the central nervous system, are far more active in the healthy brain than previously thought. Microglia facilitate many stages of brain development by shaping neuronal connectivity via synaptic elimination. Dysfunction of these same processes likely underlies a wide range of neurological and neurodevelopmental disorders.

Glucuronyl 3-sulfate occurs exclusively on distal unmyelinated terminals of selected sensory neurons in the peripheral nervous system

1995 ◽  
Vol 53 ◽  
pp. 958-959
Author(s):  
S.S. Spicer ◽  
B.A. Schulte
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Sensory Nerves ◽  
Tissue Antigens ◽  
The Central Nervous System ◽  
The Brain ◽  
Leu 7

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.

Bone-brain crosstalk and potential associated diseases

2016 ◽  
Vol 28 (2) ◽  
Author(s):  
Audrey Rousseaud ◽  
Stephanie Moriceau ◽  
Mariana Ramos-Brossier ◽  
Franck Oury
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Cognitive Functions ◽  
Intimate Relationship ◽  
Whole Body ◽  
Reciprocal Relationships ◽  
Skeletal Homeostasis ◽  
The Central Nervous System ◽  
The Brain

AbstractReciprocal relationships between organs are essential to maintain whole body homeostasis. An exciting interplay between two apparently unrelated organs, the bone and the brain, has emerged recently. Indeed, it is now well established that the brain is a powerful regulator of skeletal homeostasis via a complex network of numerous players and pathways. In turn, bone via a bone-derived molecule, osteocalcin, appears as an important factor influencing the central nervous system by regulating brain development and several cognitive functions. In this paper we will discuss this complex and intimate relationship, as well as several pathologic conditions that may reinforce their potential interdependence.

scholarly journals Tuberin levels during cellular differentiation in brain development

2021 ◽  
Author(s):  
Bashaer Abu Khatir ◽  
Gordon Omar Davis ◽  
Mariam Sameem ◽  
Rutu Patel ◽  
Jackie Fong ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Cell Lines ◽  
Neural Development ◽  
Time Course ◽  
Embryonic Mouse ◽  
Organ Systems ◽  
The Central Nervous System

Tuberin is a member of a large protein complex, Tuberous Sclerosis Complex, and acts as a sensor for nutrient status regulating protein synthesis and cell cycle progression. Mutations in the Tuberin gene, TSC2, lead to the formation of tumors and developmental defects in many organ systems, including the central nervous system. Tuberin is expressed in the brain throughout development and levels of Tuberin have been found to decrease during neuronal differentiation in cell lines in vitro. Our current work investigates the levels of Tuberin at two stages of embryonic development in vivo, and we study the mRNA and protein levels during a time course using immortalized cell lines in vitro. Our results show that Tuberin levels remain stable in the olfactory bulb but decrease in the Purkinje cell layer during embryonic mouse brain development. We show here that Tuberin levels are higher when cells are cultured as neurospheres, and knockdown of Tuberin results in a reduction in the number of neurospheres. These data provide support for the hypothesis that Tuberin is an important regulator of stemness and the reduction of Tuberin levels might support functional differentiation in the central nervous system. Understanding how Tuberin expression is regulated throughout neural development is essential to fully comprehend the role of this protein in several developmental and neural pathologies.

Developmental Overview of Central Neuroanatomy

2017 ◽  
Author(s):  
Peggy Mason
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Neural Tube ◽  
The Central Nervous System ◽  
Dorsal Telencephalon ◽  
Adult Spinal Cord ◽  
The Brain

The central nervous system develops from a proliferating tube of cells and retains a tubular organization in the adult spinal cord and brain, including the forebrain. Failure of the neural tube to close at the front is lethal, whereas failure to close the tube at the back end produces spina bifida, a serious neural tube defect. Swellings in the neural tube develop into the hindbrain, midbrain, diencephalon, and telencephalon. The diencephalon sends an outpouching out of the cranium to form the retina, providing an accessible window onto the brain. The dorsal telencephalon forms the cerebral cortex, which in humans is enormously expanded by growth in every direction. Running through the embryonic neural tube is an internal lumen that becomes the cerebrospinal fluid–containing ventricular system. The effects of damage to the spinal cord and forebrain are compared with respect to impact on self and potential for improvement.

Querkopf, a MYST family histone acetyltransferase, is required for normal cerebral cortex development

Development ◽  
2000 ◽  
Vol 127 (12) ◽  
pp. 2537-2548 ◽  
Author(s):  
T. Thomas ◽  
A.K. Voss ◽  
K. Chowdhury ◽  
P. Gruss
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Histone Acetyltransferase ◽  
System Development ◽  
Pyramidal Cells ◽  
Postnatal Period ◽  
Nervous System Development ◽  
Cortical Plate ◽  
Central Nervous System Development

In order to find, and mutate, novel genes required for regulation of neurogenesis in the cerebral cortex, we performed a genetic screen in mice. As the result of this screen, we created a new mouse mutant, querkopf. The querkopf mutation is due to an insertion into a MYST family histone acetyltransferase gene. Mice homozygous for the querkopf mutation have craniofacial abnormalities, fail to thrive in the postnatal period and have defects in central nervous system development. The defects in central nervous system development are particularly prominent in the cerebral cortex, which is disproportionally smaller than in wild-type mice. A large reduction in the size of the cortical plate was already apparent during embryogenesis. Homozygous mice show a lack of large pyramidal cells in layer V of the cortex, which is reflected in a reduction in the number of Otx1-positive neurons in this layer during postnatal development. Homozygous mice also show a reduction in the number of GAD67-positive interneurons throughout the cortex. Our results suggest that Querkopf is an essential component of a genetic cascade regulating cell differentiation in the cortex, probably acting in a multiprotein complex regulating chromatin structure during transcription.

Foundations of Neuropsychiatry

PEDIATRICS ◽  
1949 ◽  
Vol 3 (2) ◽  
pp. 253-253
Keyword(s):  
Central Nervous System ◽  
Blood Flow ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Cerebral Blood Flow ◽  
Harvard Medical School ◽  
Massachusetts General Hospital ◽  
Three Dimensional ◽  
The Central Nervous System ◽  
Disease Entities

Gives the facts and correlation needed to understand the simple workings of the central nervous system. Serves as a preface to start the student with three dimensional orientation towards neurology and psychiatry, leading up to a description of the principal disease entities. The chapters on cerebral blood flow, the types of neurons in the autonomic system and the motor areas of the cerebral cortex have been largely rewritten. The author is Bullard Professor of Neuropathology, Harvard Medical School and Psychiatrist in Chief, Massachusetts General Hospital.

Neurodevelopment

2012 ◽  
pp. 156-160
Author(s):  
Karl Zilles
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Genetic Factors ◽  
Neural Induction ◽  
The Central Nervous System

This chapter discusses neural induction, organogenesis of the central nervous system, histogenesis of the spinal cord, histogenesis of the brainstem and cerebellum, histogenesis of the cerebral cortex, hemispheric shape and the formation of gyri, and genetic factors during development.

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