Laminating the mammalian cortex during development: cell polarity protein function and Hippo signaling

Abdi, Khadar; Kuo, Chay T.

doi:10.1101/gad.316711.118

Cited by 6 publications

(5 citation statements)

References 11 publications

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“…Such bRG cells are more abundant in the developing human cortex than in other primates, and this is hypothesized to contribute to cortical expansion in evolution [49][50][51] . Prior studies have demonstrated that cultured NSCs exhibit features of apicobasal polarity in culture, 52,53 and we observed this in our culture system, as NSCs form rosette structures with inward-facing apical junctions marked with PARD3 by day 9 of NSC induction (Fig. 4B).…”

Section: Har Perturbations Disrupt the Expression Of Genes Involved I...supporting

confidence: 80%

Human Accelerated Regions regulate gene networks implicated in apical-to-basal neural progenitor fate transitions

Noble,

Ji,

Yim

et al. 2024

Preprint

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The evolution of the human cerebral cortex involved modifications in the composition and proliferative potential of the neural stem cell (NSC) niche during brain development. Human Accelerated Regions (HARs) exhibit a significant excess of human-specific sequence changes and have been implicated in human brain evolution. Multiple studies support that HARs include neurodevelopmental enhancers with novel activities in humans, but their biological functions in NSCs have not been empirically assessed at scale. Here we conducted a direct-capture Perturb-seq screen repressing 180 neurodevelopmentally active HARs in human iPSC-derived NSCs with single-cell transcriptional readout. After profiling >188,000 NSCs, we identified a set of HAR perturbations with convergent transcriptional effects on gene networks involved in NSC apicobasal polarity, a cellular process whose precise regulation is critical to the developmental emergence of basal radial glia (bRG), a progenitor population that is expanded in humans. Across multiple HAR perturbations, we found convergent dysregulation of specific apicobasal polarity and adherens junction regulators, includingPARD3, ABI2, SETD2, andPCM1. We found that the repression of one candidate from the screen, HAR181, as well as its target geneCADM1, disrupted apical PARD3 localization and NSC rosette formation. Our findings reveal interconnected roles for HARs in NSC biology and cortical development and link specific HARs to processes implicated in human cortical expansion.

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Section: Har Perturbations Disrupt the Expression Of Genes Involved I...supporting

confidence: 80%

Human Accelerated Regions regulate gene networks implicated in apical-to-basal neural progenitor fate transitions

Noble,

Ji,

Yim

et al. 2024

Preprint

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“…5 To date, a large number of such signals have been identified. 20,[49][50][51][52] In this review, these signals are classified into five subgroups: cell polarity, mechanical cues, cell density, soluble factors, and stress signals [53][54][55][56][57] (Fig. 3).…”

Section: Key Components Of the Hippo Pathwaymentioning

confidence: 99%

The Hippo signalling pathway and its implications in human health and diseases

Lan

et al. 2022

Sig Transduct Target Ther

146

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As an evolutionarily conserved signalling network, the Hippo pathway plays a crucial role in the regulation of numerous biological processes. Thus, substantial efforts have been made to understand the upstream signals that influence the activity of the Hippo pathway, as well as its physiological functions, such as cell proliferation and differentiation, organ growth, embryogenesis, and tissue regeneration/wound healing. However, dysregulation of the Hippo pathway can cause a variety of diseases, including cancer, eye diseases, cardiac diseases, pulmonary diseases, renal diseases, hepatic diseases, and immune dysfunction. Therefore, therapeutic strategies that target dysregulated Hippo components might be promising approaches for the treatment of a wide spectrum of diseases. Here, we review the key components and upstream signals of the Hippo pathway, as well as the critical physiological functions controlled by the Hippo pathway. Additionally, diseases associated with alterations in the Hippo pathway and potential therapies targeting Hippo components will be discussed.

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“…In the epithelium, PARD3 is localized to tight junctions in the Par complex, forming the boundary between the apical and basolateral domains. It plays a role in processes such as maintaining asymmetric cell division, apical basal polarity, and directional cell migration (Abdi and Kuo 2018;Li, et al 2019). It is well known that PARD3 is an important gene regulating polarity, and loss of cell polarity is a feature of advanced and aggressive cancers.…”

Section: Discussionmentioning

confidence: 99%

Partition defective 3 promotes TAZ nuclear localization and promotes Amphiregulin transcription to promote liver hepatocellular carcinoma cell invasion, migration and epithelial mesenchymal

Wang

et al. 2022

Preprint

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Background Partition defective 3 (PARD3) regulates cell polarity and functions as a cancer promoting or tumor suppressor in different cancer types. PARD3 was reported to be highly expressed in liver hepatocellular carcinoma (LIHC) tissues and high expression of PARD3 was significantly associated with poor clinicopathological features and lower overall survival, but whether PARD3 regulated invasion, migration and epithelial mesenchymal transition (EMT) in LIHC has not been reported. Objectives To investigate the effect and mechanism of PARD3 on LIHC cell invasion, migration and EMT. Methods PARD3 expression in LIHC tumor group and relationship with survival were queried according to the GEPIA website. PARD3 mRNA and protein expression in 41 clinical samples were determined by RT-qPCR and immunohistochemistry (IHC), respectively. PARD3, transcriptional coactivator with PDZ-binding motif (TAZ)and amphiregulin ༈AREG༉expression in HepG2 cells with overexpression or knockdown, and the expression of PARD3, TAZ, AREG and EMT related proteins were determined by Western blot. Transwell assay for HepG2cell invasion ability. The migration ability of HepG2 cells was detected by wound healing experiments. TAZ localization was detected by immunofluorescence. Co-IP detected the effect of PARD3 on TAZ and TAZ TEAD binding. The effect of TAZ on AREG transcript levels was examined by RT-qPCR. Results PARD3 was found to be highly expressed in LIHC tumor group by GEPIA website query, and the expression of PARD3 gradually increased with increasing tumor stage, and high expression of PARD3 usually means low overall survival in LIHC. We also found that PARD3 was highly expressed in LIHC tissues. Knockdown of PARD3 inhibited HepG2 cell invasion, migration and EMT, while overexpression of PARD3 played the opposite role. Moreover, PARD3 promotes AREG transcription by promoting TAZ nuclear localization, which in turn promotes LIHC cell invasion, migration and EMT. Conclusion PARD3 promotes TAZ nuclear localization and promotes AREG transcription to promote epithelial mesenchymal transition in LIHC.

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Laminating the mammalian cortex during development: cell polarity protein function and Hippo signaling

Cited by 6 publications

References 11 publications

Human Accelerated Regions regulate gene networks implicated in apical-to-basal neural progenitor fate transitions

Human Accelerated Regions regulate gene networks implicated in apical-to-basal neural progenitor fate transitions

The Hippo signalling pathway and its implications in human health and diseases

Partition defective 3 promotes TAZ nuclear localization and promotes Amphiregulin transcription to promote liver hepatocellular carcinoma cell invasion, migration and epithelial mesenchymal

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