Retinoic Acid from the Meninges Regulates Cortical Neuron Generation

Siegenthaler, Julie A.; Ashique, Amir M.; Zarbalis, Konstantinos; Patterson, Katelin P.; Hecht, Jonathan H.; Kane, Maureen A.; Folias, Alexandra E.; Choe, Youngshik; May, S. Randolph; Kume, Tsutomu; Napoli, Joseph L.; Peterson, Andrew S.; Pleasure, Samuel J.

doi:10.1016/j.cell.2011.07.011

Cited by 47 publications

(80 citation statements)

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“…This is clearly earlier than definitive bone marrow hematopoiesis, which commences after E15 (Ratajczak, 2008) and occurs around the time when the first definitive hematopoietic progenitors are seen in the aorta‐gonad‐mesonephros (AGM) region, at E10.5 (de Bruijn et al, 2000). Prior to that time, hematopoietic cells derive from the yolk sac, which is the site of primitive hematopoiesis (Shepard and Zon 2000). Thus, it is possible that the microglia seen in the embryonic brain originate from yolk sac‐derived monocytic precursors, which some reports indicate are first established in the neural tube as early as E8 (Naito, 1993; for review see Perry and Gordon, 1988).…”

Section: Discussionmentioning

confidence: 99%

“…The study of these various cortical precursor populations has led to the conclusion that both the timing and the magnitude of cell genesis are largely regulated by factors encountered within the developing cortical environment (Miller and Gauthier, 2007). These environmental signals derive from multiple sources, including newly born neurons (Barnabé‐Heider et al, 2005) and glial cells (Christopherson et al, 2005), meningeal cells (Radakovits et al, 2009; Siegenthaler et al, 2009), blood vessels (Shen et al, 2004; Snapyan et al, 2009), cerebrospinal fluid (Martin et al, 2006; Salehi et al, 2009) and even the precursors themselves (Barnabé‐Heider and Miller, 2003). However, one bioactive cell population that is present within the embryonic brain and that has not been addressed in this regard is the microglia, which derive from the hematopoietic system, migrate to the neural tube during midembryogenesis, and are present within the embryonic brain as early as E10.5 in the mouse (Perry et al, 1985; Ashwell, 1991; Ling and Wong, 1993; Andjelkovic et al, 1998; Hirasawa et al, 2005).…”

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confidence: 99%

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Endogenous microglia regulate development of embryonic cortical precursor cells

et al. 2011

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Microglia play important roles in the damaged or degenerating adult nervous system. However, the role of microglia in embryonic brain development is still largely uncharacterized. Here we show that microglia are present in regions of the developing brain that contain neural precursors from E11 onward. To determine whether these microglia are important for neural precursor maintenance or self-renewal, we cultured embryonic neural precursors from the cortex of PU.1(-/-) mice, which we show lack resident microglia during embryogenesis. Cell survival and neurogenesis were similar in cultures from PU.1(-/-) vs. PU.1(+/+) mice, but precursor proliferation and astrogenesis were both reduced. Cortical precursors depleted of microglia also displayed decreased precursor proliferation and astrogenesis, and these deficits could be rescued when microglia were added back to the cultures. Moreover, when the number of microglia present in cortical precursor cultures was increased above normal levels, astrogenesis but not neurogenesis was increased. Together these results demonstrate that microglia present within the embryonic neural precursor niche can regulate neural precursor development and suggest that alterations in microglial number as a consequence of genetic or pathological events could perturb neural development by directly affecting embryonic neural precursors.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Endogenous microglia regulate development of embryonic cortical precursor cells

et al. 2011

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“…Ultrasound abnormalities and serologic tests were in favor of seroconversion during the first trimester in 5 cases (Table 1); it is worth noting that Cases 4 and 10 did not display any significant brain anomaly (Table 4). Experimental data suggest that meningitis associated with the disruption of the glia limitans may disturb the trophic function of the meninges; indeed, meningeal cells can influence cell proliferation and neuronal differentiation (13,14). Although neurogenesis and neuronal migration end before 25 gestational weeks, chronic infection may explain the extent of cortical lesions.…”

Section: Neuropathologic Substrates Of Cortical Abnormalities and Assmentioning

confidence: 99%

Cytomegalovirus-Induced Brain Malformations in Fetuses

Teissier

Fallet-Bianco²,

Delezoide

et al. 2014

Journal of Neuropathology & Experimental Neurology

134

107

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Neurologic morbidity associated with congenital cytomegalovirus (CMV) infection is a major public health concern. The pathogenesis of cerebral lesions remains unclear. We report the neuropathologic substrates, the immune response, and the cellular targets of CMV in 16 infected human fetal brains aged 23 to 28.5 gestational weeks. Nine cases were microcephalic, 10 had extensive cortical lesions, 8 had hippocampal abnormalities, and 5 cases showed infection of the olfactory bulb. The density of CMV-immunolabeled cells correlated with the presence of microcephaly and the extent of brain abnormalities. Innate and adaptive immune responses were present but did not react against all CMV-infected cells. Cytomegalovirus infected all cell types but showed higher tropism for stem cells/radial glial cells. The results indicate that 2 main factors influence the neuropathologic outcome at this stage: the density of CMV-positive cells and the tropism of CMV for stem/progenitor cells. This suggests that the large spectrum of CMV-induced brain abnormalities is caused not only by tissue destruction but also by the particular vulnerability of stem cells during early brain development. Florid infection of the hippocampus and the olfactory bulb may expose these patients to the risk of neurocognitive and sensorineural handicap even in cases of infection at late stages of gestation.

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“…The meninges comprise three distinct cellular layers covering the brain: the outer dura contacts the inner table of the skull, the inner pia adheres to the surface of the brain, and the netlike fibers of the arachnoid connect the two3. The meninges produce important regulatory factors for brain and skull development including CXCL12, regulating Cajal-Retzius cell and interneuron migration4-7, TGF-β and FGF-2, regulating skull development8, 9, and all-trans retinoic acid, regulating cortical neurogenesis10.…”

Section: Introductionmentioning

confidence: 99%

Primary cellular meningeal defects cause neocortical dysplasia and dyslamination

Hecht

Siegenthaler

Patterson

et al. 2010

Annals of Neurology

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Objective Cortical malformations are important causes of neurological morbidity, but in many cases their etiology is poorly understood. Mice with Foxc1 mutations have cellular defects in meningeal development. We use hypomorphic and null alleles of Foxc1 to study the effect of meningeal defects on neocortical organization. Methods Embryos with loss of Foxc1 activity were generated using the hypomorphic Foxc1hith allele and the null Foxc1lacZ allele. Immunohistologic analysis was used to assess cerebral basement membrane integrity, marginal zone heterotopia formation, neuronal overmigration, meningeal defects, and changes in basement membrane composition. Dysplasia severity was quantified using two measures. Results Cortical dysplasia resembling cobblestone cortex, with basement membrane breakdown and lamination defects, is seen in Foxc1 mutants. As Foxc1 activity was reduced, abnormalities in basement membrane integrity, heterotopia formation, neuronal overmigration, and meningeal development appeared earlier in gestation and were more severe. Surprisingly, the basement membrane appeared intact at early stages of development in the face of severe deficits in meningeal development. Prominent defects in basement membrane integrity appeared as development proceeded. Molecular analysis of basement membrane laminin subunits demonstrated that loss of the meninges led to changes in basement membrane composition. Interpretation Cortical dysplasia can be caused by cellular defects in the meninges. The meninges are not required for basement membrane establishment but are needed for remodeling as the brain expands. Specific changes in basement membrane composition may contribute to subsequent breakdown. Our study raises the possibility that primary meningeal defects may cortical dysplasia in some cases.

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Retinoic Acid from the Meninges Regulates Cortical Neuron Generation

Cited by 47 publications

References 0 publications

Endogenous microglia regulate development of embryonic cortical precursor cells

Endogenous microglia regulate development of embryonic cortical precursor cells

Cytomegalovirus-Induced Brain Malformations in Fetuses

Primary cellular meningeal defects cause neocortical dysplasia and dyslamination

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