Neural crest mechanosensors: Seeing old proteins in a new light

Coutiño, Brenda Canales; Mayor, Roberto

doi:10.1016/j.devcel.2022.07.005

Cited by 8 publications

(6 citation statements)

References 123 publications

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“…Our results showing genipin’s ability to rescue neurodevelopmental defects in hPSC-derived FD SNs and in SNs in mice highlight the importance of ECM proteins during development. This data lays the groundwork to further investigate the ECM composition necessary for normal PNS development, as well as how defects in ECM proteins, such as laminin 17 , contribute to PNS disorders 67 . The rescue on neurodevelopment that we see in FD mice is interesting and urges the investigation of the effects of genipin on neurodegeneration further.…”

Section: Discussionmentioning

confidence: 88%

“…We hypothesized that YAP activation initiates a transcriptional program that allows the proliferation of progenitor cells, thus increasing the number and survival of SNs. Very little is known of the role of the Hippo pathway and YAP function in the PNS, although mechanotransduction (including ECM-cell interaction) is important in NC migration and differentiation 67 . Furthermore, it has been proposed that mechanical modulation of the Hippo pathway could potentially be used as a treatment for peripheral neuropathies 73 .…”

Section: Discussionmentioning

confidence: 99%

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Genipin Crosslinks the Extracellular Matrix to Rescue Developmental and Degenerative Defects, and Accelerates Regeneration of Peripheral Neurons

Saito-Diaz

Dietrich

et al. 2023

Preprint

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The peripheral nervous system (PNS) is essential for proper body function. A high percentage of the population suffer nerve degeneration or peripheral damage. For example, over 40% of patients with diabetes or undergoing chemotherapy develop peripheral neuropathies. Despite this, there are major gaps in the knowledge of human PNS development and therefore, there are no available treatments. Familial Dysautonomia (FD) is a devastating disorder that specifically affects the PNS making it an ideal model to study PNS dysfunction. FD is caused by a homozygous point mutation in ELP1 leading to developmental and degenerative defects in the sensory and autonomic lineages. We previously employed human pluripotent stem cells (hPSCs) to show that peripheral sensory neurons (SNs) are not generated efficiently and degenerate over time in FD. Here, we conducted a chemical screen to identify compounds able to rescue this SN differentiation inefficiency. We identified that genipin, a compound prescribed in Traditional Chinese Medicine for neurodegenerative disorders, restores neural crest and SN development in FD, both in the hPSC model and in a FD mouse model. Additionally, genipin prevented FD neuronal degeneration, suggesting that it could be offered to patients suffering from PNS neurodegenerative disorders. We found that genipin crosslinks the extracellular matrix, increases the stiffness of the ECM, reorganizes the actin cytoskeleton, and promotes transcription of YAP-dependent genes. Finally, we show that genipin enhances axon regeneration in an in vitro axotomy model in healthy sensory and sympathetic neurons (part of the PNS) and in prefrontal cortical neurons (part of the central nervous system, CNS). Our results suggest genipin can be used as a promising drug candidate for treatment of neurodevelopmental and neurodegenerative diseases, and as a enhancer of neuronal regeneration.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Genipin Crosslinks the Extracellular Matrix to Rescue Developmental and Degenerative Defects, and Accelerates Regeneration of Peripheral Neurons

Saito-Diaz

Dietrich

et al. 2023

Preprint

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“…As mentioned, mesenchymal stem cells responsible for continuous growth on the murine tooth originate from neural crest cells [ 5 , 16 ]. During development, neural crest cells exhibit durotaxis—migration in a gradient of stiffness from a softer to stiffer environment [ 17 ]. Consequently, neural crest cell differentiation is stiffness-dependent.…”

Section: Mechanical Cues In the Physiology And Pathology Of Dental Pulpmentioning

confidence: 99%

Mechanobiology of Dental Pulp Cells

Bryniarska-Kubiak,

Basta-Kaim,

Kubiak

2024

Cells

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The dental pulp is the inner part of the tooth responsible for properly functioning during its lifespan. Apart from the very big biological heterogeneity of dental cells, tooth microenvironments differ a lot in the context of mechanical properties—ranging from 5.5 kPa for dental pulp to around 100 GPa for dentin and enamel. This physical heterogeneity and complexity plays a key role in tooth physiology and in turn, is a great target for a variety of therapeutic approaches. First of all, physical mechanisms are crucial for the pain propagation process from the tooth surface to the nerves inside the dental pulp. On the other hand, the modulation of the physical environment affects the functioning of dental pulp cells and thus is important for regenerative medicine. In the present review, we describe the physiological significance of biomechanical processes in the physiology and pathology of dental pulp. Moreover, we couple those phenomena with recent advances in the fields of bioengineering and pharmacology aiming to control the functioning of dental pulp cells, reduce pain, and enhance the differentiation of dental cells into desired lineages. The reviewed literature shows great progress in the topic of bioengineering of dental pulp—although mainly in vitro. Apart from a few positions, it leaves a gap for necessary filling with studies providing the mechanisms of the mechanical control of dental pulp functioning in vivo.

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“…[ 22 ] Mechanical forces could affect the collective migration and differentiation of NC cells. [ 23 ] During the initial morphogenesis, mesoderm stiffness was found to initiate an epithelial‐to‐mesenchymal transition in Xenopus NC cells and then triggered their collective migration. [ 24 ] Similarly, Shellard and Mayor reported that Xenopus NC cell migration was impacted by the self‐generated stiffness gradient in the placode tissue, showing impaired NC migration when the stiffness gradient was completely abrogated.…”

Section: Physical Microenvironment In Neurogenesis Neurodevelopment A...mentioning

confidence: 99%

Engineering the Physical Microenvironment into Neural Organoids for Neurogenesis and Neurodevelopment

Li,

Sun,

Hou

et al. 2023

Small

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Understanding the signals from the physical microenvironment is critical for deciphering the processes of neurogenesis and neurodevelopment. The discovery of how surrounding physical signals shape human developing neurons is hindered by the bottleneck of conventional cell culture and animal models. Notwithstanding neural organoids provide a promising platform for recapitulating human neurogenesis and neurodevelopment, building neuronal physical microenvironment that accurately mimics the native neurophysical features is largely ignored in current organoid technologies. Here, it is discussed how the physical microenvironment modulates critical events during the periods of neurogenesis and neurodevelopment, such as neural stem cell fates, neural tube closure, neuronal migration, axonal guidance, optic cup formation, and cortical folding. Although animal models are widely used to investigate the impacts of physical factors on neurodevelopment and neuropathy, the important roles of human stem cell‐derived neural organoids in this field are particularly highlighted. Considering the great promise of human organoids, building neural organoid microenvironments with mechanical forces, electrophysiological microsystems, and light manipulation will help to fully understand the physical cues in neurodevelopmental processes. Neural organoids combined with cutting‐edge techniques, such as advanced atomic force microscopes, microrobots, and structural color biomaterials might promote the development of neural organoid‐based research and neuroscience.

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Neural crest mechanosensors: Seeing old proteins in a new light

Cited by 8 publications

References 123 publications

Genipin Crosslinks the Extracellular Matrix to Rescue Developmental and Degenerative Defects, and Accelerates Regeneration of Peripheral Neurons

Genipin Crosslinks the Extracellular Matrix to Rescue Developmental and Degenerative Defects, and Accelerates Regeneration of Peripheral Neurons

Mechanobiology of Dental Pulp Cells

Engineering the Physical Microenvironment into Neural Organoids for Neurogenesis and Neurodevelopment

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