Yap/Taz are required for establishing the cerebellar radial glia scaffold and proper foliation

Hughes, Lucinda J.; Park, Raehee; Lee, Min Jung; Terry, Bethany K.; Lee, Dong Hoon; Kim, Hansol; Cho, Seo‐Hee; Kim, Seonhee

doi:10.1016/j.ydbio.2019.10.002

Cited by 8 publications

(20 citation statements)

References 60 publications

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“…Whether YAP contributed to the expansion of the oRG population in gyrencephalic species over the course of evolution remains to be determined. One study showed that YAP/TAZ are required for the junctional integrity of the cerebellar neuroepithelium (Hughes et al, 2020), which is similar to our finding in the cortex.…”

Section: Discussionsupporting

confidence: 90%

YAP/TAZ Maintain the Proliferative Capacity and Structural Organization of Radial Glial Cells During Brain Development

Lavado

Gangwar

Paré

et al. 2021

Preprint

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The Hippo pathway regulates the development and homeostasis of many tissues and in many species. It controls the activity of two paralogous transcriptional coactivators, YAP and TAZ (YAP/TAZ). Although previous studies have established that aberrant YAP/TAZ activation is detrimental to mammalian brain development, whether and how endogenous levels of YAP/TAZ activity regulate brain development remain unclear. Here, we show that during mammalian cortical development, YAP/TAZ are specifically expressed in apical neural progenitor cells known as radial glial cells (RGCs). The subcellular localization of YAP/TAZ undergoes dynamic changes as corticogenesis proceeds. YAP/TAZ are required for maintaining the proliferative potential and structural organization of RGCs, and their ablation during cortical development reduces the numbers of cortical projection neurons and causes the loss of ependymal cells, resulting in hydrocephaly. Transcriptomic analysis using sorted RGCs reveals gene expression changes in YAP/TAZ-depleted cells that correlate with mutant phenotypes. Thus, our study has uncovered essential functions of YAP/TAZ during mammalian brain development and revealed the transcriptional mechanism of their action.

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Section: Discussionsupporting

confidence: 90%

YAP/TAZ Maintain the Proliferative Capacity and Structural Organization of Radial Glial Cells During Brain Development

Lavado

Gangwar

Paré

et al. 2021

Preprint

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“…In the absence of NF2, there is an elevated YAP1 activity in the NPCs, which disrupt the formation of guidepost cells and results in dysplasia of the corpus callosum (Lavado et al., 2014). Loss of Yap/Taz in the cerebellum, as demonstrated in a study on double knockout mouse model, results in reduced cerebellar size accompanied with defects in foliation and fissure formation (Hughes et al., 2020). Interestingly, a recent study has demonstrated that under high glucose conditions, human NPCs exhibit alteration in the DNA methylation status of some key pathway genes, including Hippo signaling (Kandilya et al., 2020), which could serve as the basis for neurodevelopmental deformities reported in the offspring of diabetic pregnancy.…”

Section: Hippo/yap Signaling In Neurodevelopmental and Neurodegeneratmentioning

confidence: 99%

“…In cerebellar granule precursor cells, AMOG negatively regulates the expression of Nf2, leading to increased YAP activity, and hence, actin cytoskeleton reorganization in a manner suitable for cerebellar development (Litan et al., 2019). Another important role of the Hippo signaling effector Yap/Taz is in guiding cerebellar morphogenesis, specifically in the development of secondary fissure and proper foliation of the cerebellum (Hughes et al., 2020).…”

Section: Hippo/yap Signaling In Brain Developmentmentioning

confidence: 99%

Neuronal Hippo signaling: From development to diseases

Sahu

Mondal

2020

Developmental Neurobiology

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Hippo signaling pathway is a highly conserved and familiar tissue growth regulator, primarily dealing with cell survival, cell proliferation, and apoptosis. The Yes‐associated protein (YAP) is the key transcriptional effector molecule, which is under negative regulation of the Hippo pathway. Wealth of studies have identified crucial roles of Hippo/YAP signaling pathway during the process of development, including the development of neuronal system. We provide here, an overview of the contributions of this signaling pathway at multiple stages of neuronal development including, proliferation of neural stem cells (NSCs), migration of NSCs toward their destined niche, maintaining NSCs in the quiescent state, differentiation of NSCs into neurons, neuritogenesis, synaptogenesis, brain development, and in neuronal apoptosis. Hyperactivation of the neuronal Hippo pathway can also lead to a variety of devastating neurodegenerative diseases. Instances of aberrant Hippo pathway leading to neurodegenerative diseases along with the approaches utilizing this pathway as molecular targets for therapeutics has been highlighted in this review. Recent evidences suggesting neuronal repair and regenerative potential of this pathway has also been pointed out, that will shed light on a novel aspect of Hippo pathway in regenerative medicine. Our review provides a better understanding of the significance of Hippo pathway in the journey of neuronal system from development to diseases as a whole.

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“…75 Interestingly, YAP/TAZ are also highly expressed in choroid plexus cells. 49,57 Choroid plexus cells, which produce CSF, begin to develop around E12.5 in mice and around 6 weeks post-conception in humans. 76 To the best of our knowledge, however, the role of YAP/TAZ in choroid plexus function and development has received little attention and remains to be investigated.…”

Section: Yap/taz Function In Ventricular System Developmentmentioning

confidence: 99%

The role of Hippo‐YAP/TAZ signaling in brain development

Terry

Kim

2022

Developmental Dynamics

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In order for our complex nervous system to develop normally, both precise spatial and temporal regulation of a number of different signaling pathways is critical. During both early embryogenesis and in organ development, one pathway that has been repeatedly implicated is the Hippo-YAP/TAZ signaling pathway. The paralogs YAP and TAZ are transcriptional co-activators that play an important role in cell proliferation, cell differentiation, and organ growth.Regulation of these proteins by the Hippo kinase cascade is therefore important for normal development. In this article, we review the growing field of research surrounding the role of Hippo-YAP/TAZ signaling in normal and atypical brain development. Starting from the development of the neural tube to the development and refinement of the cerebral cortex, cerebellum, and ventricular system, we address the typical role of these transcriptional co-activators, the functional consequences that manipulation of YAP/TAZ and their upstream regulators have on brain development, and where further research may be of benefit.

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Yap/Taz are required for establishing the cerebellar radial glia scaffold and proper foliation

Cited by 8 publications

References 60 publications

YAP/TAZ Maintain the Proliferative Capacity and Structural Organization of Radial Glial Cells During Brain Development

YAP/TAZ Maintain the Proliferative Capacity and Structural Organization of Radial Glial Cells During Brain Development

Neuronal Hippo signaling: From development to diseases

The role of Hippo‐YAP/TAZ signaling in brain development

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