Pten regulates neural crest proliferation and differentiation during mouse craniofacial development

Yang, Tianfang; Moore, M.; He, Fenglei

doi:10.1002/dvdy.24605

Cited by 12 publications

(19 citation statements)

References 33 publications

(46 reference statements)

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“…Furthermore, we attempted to investigate PTEN expression, which is involved in PI3K/mTOR pathway and is implicated in craniofacial morphogenesis in mice. 61 We observed increased PTEN A recent study has related PTEN to osteogenesis, claiming that high levels of PTEN were responsible for the osteoblastic potential of human dental pulp cells (DP-MSCs). 63 In our study, untreated cranial cells present PTEN expression but no AKT phosphorylation, which is in accordance with previous studies indicating that abundant levels of PTEN normally maintain AKT in an inactive form in osteoblastic cells.…”

Section: Discussionmentioning

confidence: 59%

Polycystin‐1 regulates cell proliferation and migration through AKT/mTORC2 pathway in a human craniosynostosis cell model

Katsianou

Papavassiliou

Gargalionis

et al. 2022

J Cellular Molecular Medi

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Craniosynostosis is the premature fusion of skull sutures and has a severe pathological impact on childrens' life. Mechanical forces are capable of triggering biological responses in bone cells and regulate osteoblastogenesis in cranial sutures, leading to premature closure. The mechanosensitive proteins polycystin-1 (PC1) and polycystin-2 (PC2) have been documented to play an important role in craniofacial proliferation and development. Herein, we investigated the contribution of PC1 to the pathogenesis of non-syndromic craniosynostosis and the associated molecular mechanisms. Protein expression of PC1 and PC2 was detected in bone fragments derived from craniosynostosis patients via immunohistochemistry. To explore the modulatory role of PC1 in primary cranial suture cells, we further abrogated the function of PC1 extracellular mechanosensing domain using a specific anti-PC1 IgPKD1 antibody. Effect of IgPKD1 treatment was evaluated with cell proliferation and migration assays. Activation of PI3K/AKT/mTOR pathway components was further detected via Western blot in primary cranial suture cells following IgPKD1 treatment. PC1 and PC2 are expressed in human tissues of craniosynostosis. PC1 functional inhibition resulted in elevated proliferation and migration of primary cranial suture cells. PC1 inhibition also induced activation of AKT, exhibiting elevated phospho (p)-AKT (Ser473) levels, but not 4EBP1 or p70S6K activation. Our findings indicate that PC1 may act as a mechanosensing molecule in cranial sutures by modulating osteoblastic cell proliferation and migration through the PC1/AKT/mTORC2 cascade with a potential impact on the development of non-syndromic craniosynostosis.

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Section: Discussionmentioning

confidence: 59%

Polycystin‐1 regulates cell proliferation and migration through AKT/mTORC2 pathway in a human craniosynostosis cell model

Katsianou

Papavassiliou

Gargalionis

et al. 2022

J Cellular Molecular Medi

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“…Inactivation of PTEN in neural crest cells leads to craniofacial malformation due to altered cell proliferation and differentiation. 122 Mechanistically, PTEN abundance is modulated by the NUMB endocytic adaptor protein via the posttranslational ubiquitin–proteasome pathway in osteoblastic cells. 123 …”

Section: Ptps In Osteoblast Development Function and Bone Homeostasismentioning

confidence: 99%

Protein tyrosine phosphatases in skeletal development and diseases

et al. 2022

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Skeletal development and homeostasis in mammals are modulated by finely coordinated processes of migration, proliferation, differentiation, and death of skeletogenic cells originating from the mesoderm and neural crest. Numerous molecular mechanisms are involved in these regulatory processes, one of which is protein posttranslational modifications, particularly protein tyrosine phosphorylation (PYP). PYP occurs mainly through the action of protein tyrosine kinases (PTKs), modifying protein enzymatic activity, changing its cellular localization, and aiding in the assembly or disassembly of protein signaling complexes. Under physiological conditions, PYP is balanced by the coordinated action of PTKs and protein tyrosine phosphatases (PTPs). Dysregulation of PYP can cause genetic, metabolic, developmental, and oncogenic skeletal diseases. Although PYP is a reversible biochemical process, in contrast to PTKs, little is known about how this equilibrium is modulated by PTPs in the skeletal system. Whole-genome sequencing has revealed a large and diverse superfamily of PTP genes (over 100 members) in humans, which can be further divided into cysteine (Cys)-, aspartic acid (Asp)-, and histidine (His)-based PTPs. Here, we review current knowledge about the functions and regulatory mechanisms of 28 PTPs involved in skeletal development and diseases; 27 of them belong to class I and II Cys-based PTPs, and the other is an Asp-based PTP. Recent progress in analyzing animal models that harbor various mutations in these PTPs and future research directions are also discussed. Our literature review indicates that PTPs are as crucial as PTKs in supporting skeletal development and homeostasis.

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“…BrdU assays indicated an increase in proliferation in this region, though additional effects on migration and differentiation cannot be ruled out (He and Soriano, 2017). Furthermore, loss of Pten in NCCs caused enhanced PI3K-AKT signaling and subsequent overgrowth of tissue (T. Yang et al, 2017).…”

Section: Mapk Pathwaysmentioning

confidence: 99%

“…There are also several reports pointing to PI3K as a regulator of NCC differentiation. One recent study ablated the negative regulator Pten in NC, resulting in enhanced proliferation as well as osteoblast differentiation in cephalic NCCs (T. Yang et al, 2017).…”

Section: Mapk Pathwaysmentioning

confidence: 99%

MAPK and PI3K signaling: At the crossroads of neural crest development

Dinsmore

Soriano

2018

Developmental Biology

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Receptor tyrosine kinase-mediated growth factor signaling is essential for proper formation and development of the neural crest. The many ligands and receptors implicated in these processes signal through relatively few downstream pathways, frequently converging on the MAPK and PI3K pathways. Despite decades of study, there is still considerable uncertainty about where and when these signaling pathways are required and how they elicit particular responses. This review summarizes our current understanding of growth factor-induced MAPK and PI3K signaling in the neural crest.

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Pten regulates neural crest proliferation and differentiation during mouse craniofacial development

Cited by 12 publications

References 33 publications

Polycystin‐1 regulates cell proliferation and migration through AKT/mTORC2 pathway in a human craniosynostosis cell model

Polycystin‐1 regulates cell proliferation and migration through AKT/mTORC2 pathway in a human craniosynostosis cell model

Protein tyrosine phosphatases in skeletal development and diseases

MAPK and PI3K signaling: At the crossroads of neural crest development

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