Expression of Pax2 protein during the formation of the central nervous system in human embryos

Namm, Aimar; Arend, Andres; Aunapuu, Marina

doi:10.5603/fm.2014.0043

Cited by 10 publications

(5 citation statements)

References 14 publications

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“…26 Recently, PAX2 has been reported to be expressed during the formation of the central nervous system in human embryos. 27 Our study allows to localize PAX2 expression in the precursor cells of subventricular zone, in the migrating neurons of the intermediate zone and in the postmitotic neurons in the cortical plate. These findings may suggest a possible role for PAX2 in neuronal migration and differentiation.…”

Section: Discussionmentioning

confidence: 97%

Immunohistochemical markers of neural progenitor cells in the early embryonic human cerebral cortex

et al. 2016

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The development of the human central nervous system represents a delicate moment of embryogenesis. The purpose of this study was to analyze the expression of multiple immunohistochemical markers in the stem/progenitor cells in the human cerebral cortex during the early phases of development. To this end, samples from cerebral cortex were obtained from 4 human embryos of 11 weeks of gestation. Each sample was formalin-fixed, paraffin embedded and immunostained with several markers including GFAP, WT1, Nestin, Vimentin, CD117, S100B, Sox2, PAX2, PAX5, Tβ4, Neurofilament, CD44, CD133, Synaptophysin and Cyclin D1. Our study shows the ability of the different immunohistochemical markers to evidence different zones of the developing human cerebral cortex, allowing the identification of the multiple stages of differentiation of neuronal and glial precursors. Three important markers of radial glial cells are evidenced in this early gestational age: Vimentin, Nestin and WT1. Sox2 was expressed by the stem/progenitor cells of the ventricular zone, whereas the postmitotic neurons of the cortical plate were immunostained by PAX2 and NSE. Future studies are needed to test other important stem/progenitor cells markers and to better analyze differences in the immunohistochemical expression of these markers during gestation.

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Section: Discussionmentioning

confidence: 97%

Immunohistochemical markers of neural progenitor cells in the early embryonic human cerebral cortex

et al. 2016

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“…While the genetic heterogeneity and intricacy of RRBs has complicated the question of pathophysiological mechanisms, abundant evidence suggests that transcription factors play an important role in the process of neurodevelopmental disorders. 17 , 18 Pax2 is one of the transcription factors expressed in many tissues, 8 , 19 and mutations in Pax2 lead to many diseases. 9 , 10 , 11 , 20 In previous studies, we found increased self‐grooming behavior and impaired spatial and memory abilities in Pax2 +/− mice.…”

Section: Discussionmentioning

confidence: 99%

Impaired neural circuitry of hippocampus in Pax2 nervous system‐specific knockout mice leads to restricted repetitive behaviors

Wang,

Tang

et al. 2023

CNS Neurosci Ther

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IntroductionRestricted repetitive behaviors (RRBs), which are associated with many different neurological and mental disorders, such as obsessive‐compulsive disorder (OCD) and autism, are patterns of behavior with little variation and little obvious function. Paired Box 2 (Pax2) is a transcription factor that is expressed in many systems, including the kidney and the central nervous system. The protein that is encoded by Pax2 has been implicated in the development of the nervous system and neurodevelopmental disorders. In our previous study, Pax2 heterozygous gene knockout mice (Pax2+/− mice) showed abnormally increased self‐grooming and impaired learning and memory abilities. However, it remains unclear which cell type is involved in this process. In this study, we deleted Pax2 only in the nervous system to determine the regulatory mechanism of Pax2 in RRBs.MethodsIn this study, Pax2 nervous system‐specific knockout mice (Nestin‐Pax2 mice) aged 6–8 weeks and Pax2 flox mice of the same age were recruited as the experimental group. Tamoxifen and vehicle were administered via intraperitoneal injection to induce Pax2 knockout after gene identification. Western blotting was used to detect Pax2 expression. After that, we assessed the general health of these two groups of mice. The self‐grooming test, marble burying test and T‐maze acquisition and reversal learning test were used to observe the lower‐order and higher‐order RRBs. The three‐chamber test, Y‐maze, and elevated plus‐maze were used to assess social ability, spatial memory ability, and anxiety. Neural circuitry tracing and transcriptome sequencing (RNA‐seq) were used to observe the abnormal neural circuitry, differentially expressed genes (DEGs) and signaling pathways affected by Pax2 gene knockout in the nervous system and the putative molecular mechanism.Results(1) The Nestin‐Pax2 mouse model was successfully constructed, and the Nestin‐Pax2 mice showed decreased expression of Pax2. (2) Nestin‐Pax2 mice showed increased self‐grooming behavior and impaired T‐maze reversal behavior compared with Pax2 flox mice. (3) An increased number of projection fibers can be found in the mPFC projecting to the CA1 and BLA, and a reduction in IGFBP2 can be found in the hippocampus of Nestin‐Pax2 mice.ConclusionThe results demonstrated that loss of Pax2 in the nervous system leads to restricted repetitive behaviors. The mechanism may be associated with impaired neural circuitry and a reduction in IGFBP2.

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“… 31 For example, prenatal cerebellar development is linked to homeobox genes such as PAX-2 and fibroblast growth factor 8. 32 – 34 These genes also play critical roles in early kidney development and are associated with congenital kidney anomalies, namely, disorders of nephron development, renal agenesis, and vesicoureteral reflux. 35 – 40 Considering this, we postulate a “diathesis-stress” model, wherein the presence of CKD (i.e., diathesis) renders the cerebellum particularly vulnerable to systemic sequalae (i.e., stress) associated with advancing CKD.…”

Section: Discussionmentioning

confidence: 99%

Associations between neurofilament light-chain protein, brain structure, and chronic kidney disease

et al. 2021

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Background: Neurofilament light chain (NfL) protein is a blood-based marker of neuroaxonal injury. We sought to 1) compare plasma NfL levels in children with chronic kidney disease (CKD) and healthy peers, 2) characterize the relationship between NfL level and kidney function, and 3) evaluate NfL as a predictor of abnormal brain structure in CKD. Methods: Sixteen children with CKD due to congenital kidney anomalies and 23 typically developing peers were included. Plasma NfL was quantified using single-molecule array immunoassay. Participants underwent structural magnetic resonance imaging. Multiple linear regression models were used to evaluate the association between plasma NfL levels, kidney function, and brain structure. Results: An age × group interaction was identified whereby NfL levels increased with age in the CKD group only (estimate = 0.65; CI = 0.08–1.22; p = 0.026). Decreased kidney function was associated with higher NfL levels (estimate = −0.10; CI = −0.16 to −0.04; p = 0.003). Lower cerebellar gray matter volume predicted increased plasma NfL levels (estimate = −0.00024; CI = −0.00039–0.00009; p = 0.004) within the CKD group. Conclusion: Children with CKD show accelerated age-related increase in NfL levels. NfL level is associated with lower kidney function and abnormal brain structure in CKD.

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Expression of Pax2 protein during the formation of the central nervous system in human embryos

Cited by 10 publications

References 14 publications

Immunohistochemical markers of neural progenitor cells in the early embryonic human cerebral cortex

Immunohistochemical markers of neural progenitor cells in the early embryonic human cerebral cortex

Impaired neural circuitry of hippocampus in Pax2 nervous system‐specific knockout mice leads to restricted repetitive behaviors

Associations between neurofilament light-chain protein, brain structure, and chronic kidney disease

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