Talk:Lecture - Neural Crest Development

From Embryology


Quantitative Multimodal Evaluation of Passaging Human Neural Crest Stem Cells for Peripheral Nerve Regeneration

Stem Cell Rev. 2017 Aug 5. doi: 10.1007/s12015-017-9758-9. [Epub ahead of print]

Du J1, Chen H1, Zhou K1,2, Jia X3,4,5,6,7,8.


Peripheral nerve injury is a major burden to societies worldwide, however, current therapy options (e.g. autologous nerve grafts) are unable to produce satisfactory outcomes. Many studies have shown that stem cell transplantation holds great potential for peripheral nerve repair, and human neural crest stem cells (hNCSCs), which give rise to a variety of tissues in the peripheral nervous system, are particularly promising. NCSCs are one of the best candidates for clinical translation, however, to ensure the viability and quality of NCSCs for research and clinical use, the effect of in vitro cell passaging on therapeutic effects needs be evaluated given that passaging is required to expand NCSCs to meet the demands of transplantation in preclinical research and clinical trials. To date, no study has investigated the quality of NCSCs past the 5th passage in vivo. In this study, we employed a multimodal evaluation system to investigate changes in outcomes between transplantation with 5th (p5) and 6th passage (p6) NCSCs in a 15 mm rat sciatic nerve injury and repair model. Using CatWalk gait analysis, gastrocnemius muscle index, electrophysiology, immunohistochemistry, and histomorphometric analysis, we showed that p6 NCSCs demonstrated decreased cell survival, Schwann-cell differentiation, axonal growth, and functional outcomes compared to p5 NCSCs (all p < 0.05). In conclusion, p6 NCSCs showed significantly reduced therapeutic efficacy compared to p5 NCSCs for peripheral nerve regeneration. KEYWORDS: Cell passage; Gait analysis; Human neural crest stem cell; Nerve regeneration; Peripheral nerve injury PMID 28780695 DOI: 10.1007/s12015-017-9758-9


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Lecture Date: 2013-09-10 Lecture Time: 16:00 Venue: BioMed E; Speaker: Professor Ken Ashwell The Powerpoint file used to present this lecture is available as a pdf document HERE A recording of the lecture will be available afterwards at the Echo Centre accessible via Blackboard.

Regulation of trunk myogenesis by the neural crest: a new facet of neural crest-somite interactions

Dev Cell. 2011 Aug 16;21(2):187-8.

Kalcheim C. Source Department of Medical Neurobiology, IMRIC and ELSC, Hebrew University-Hadassah Medical School, P.O. Box 12272, Jerusalem 91120, Israel.


It is well established that the somitic mesoderm regulates early stages of neural crest development and further segmentation of crest-derived peripheral ganglia. The possibility that neural crest progenitors feed back on the somites was, however, not explored. Two recent studies provide evidence that the neural crest regulates somite-derived myogenesis by distinct mechanisms.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID 21839914

Activation of FGF signaling mediates proliferative and osteogenic differences between neural crest derived frontal and mesoderm parietal derived bone

PLoS One. 2010 Nov 18;5(11):e14033.

Li S, Quarto N, Longaker MT. Source Department of Surgery, Children's Surgical Research Program, Stanford University School of Medicine, Stanford, California, USA.


BACKGROUND: As a culmination of efforts over the last years, our knowledge of the embryonic origins of the mammalian frontal and parietal cranial bones is unambiguous. Progenitor cells that subsequently give rise to frontal bone are of neural crest origin, while parietal bone progenitors arise from paraxial mesoderm. Given the unique qualities of neural crest cells and the clear delineation of the embryonic origins of the calvarial bones, we sought to determine whether mouse neural crest derived frontal bone differs in biology from mesoderm derived parietal bone.

METHODS: BrdU incorporation, immunoblotting and osteogenic differentiation assays were performed to investigate the proliferative rate and osteogenic potential of embryonic and postnatal osteoblasts derived from mouse frontal and parietal bones. Co-culture experiments and treatment with conditioned medium harvested from both types of osteoblasts were performed to investigate potential interactions between the two different tissue origin osteoblasts. Immunoblotting techniques were used to investigate the endogenous level of FGF-2 and the activation of three major FGF signaling pathways. Knockdown of FGF Receptor 1 (FgfR1) was employed to inactivate the FGF signaling.

RESULTS: Our results demonstrated that striking differences in cell proliferation and osteogenic differentiation between the frontal and parietal bone can be detected already at embryonic stages. The greater proliferation rate, as well as osteogenic capacity of frontal bone derived osteoblasts, were paralleled by an elevated level of FGF-2 protein synthesis. Moreover, an enhanced activation of FGF-signaling pathways was observed in frontal bone derived osteoblasts. Finally, the greater osteogenic potential of frontal derived osteoblasts was dramatically impaired by knocking down FgfR1.

CONCLUSIONS: Osteoblasts from mouse neural crest derived frontal bone displayed a greater proliferative and osteogenic potential and endogenous enhanced activation of FGF signaling compared to osteoblasts from mesoderm derived parietal bone. FGF signaling plays a key role in determining biological differences between the two types of osteoblasts.

PMID 21124973

Relationship between neural crest cells and cranial mesoderm during head muscle development

PLoS One. 2009;4(2):e4381. Epub 2009 Feb 9.

Grenier J, Teillet MA, Grifone R, Kelly RG, Duprez D. Source CNRS, UMR 7622 Biologie Moléculaire et Cellulaire du Développement, Université Pierre et Marie Curie, Paris, France.


BACKGROUND: In vertebrates, the skeletal elements of the jaw, together with the connective tissues and tendons, originate from neural crest cells, while the associated muscles derive mainly from cranial mesoderm. Previous studies have shown that neural crest cells migrate in close association with cranial mesoderm and then circumscribe but do not penetrate the core of muscle precursor cells of the branchial arches at early stages of development, thus defining a sharp boundary between neural crest cells and mesodermal muscle progenitor cells. Tendons constitute one of the neural crest derivatives likely to interact with muscle formation. However, head tendon formation has not been studied, nor have tendon and muscle interactions in the head.

METHODOLOGY/PRINCIPAL FINDINGS: Reinvestigation of the relationship between cranial neural crest cells and muscle precursor cells during development of the first branchial arch, using quail/chick chimeras and molecular markers revealed several novel features concerning the interface between neural crest cells and mesoderm. We observed that neural crest cells migrate into the cephalic mesoderm containing myogenic precursor cells, leading to the presence of neural crest cells inside the mesodermal core of the first branchial arch. We have also established that all the forming tendons associated with branchiomeric and eye muscles are of neural crest origin and express the Scleraxis marker in chick and mouse embryos. Moreover, analysis of Scleraxis expression in the absence of branchiomeric muscles in Tbx1(-/-) mutant mice, showed that muscles are not necessary for the initiation of tendon formation but are required for further tendon development.

CONCLUSIONS/SIGNIFICANCE: This results show that neural crest cells and muscle progenitor cells are more extensively mixed than previously believed during arch development. In addition, our results show that interactions between muscles and tendons during craniofacial development are similar to those observed in the limb, despite the distinct embryological origin of these cell types in the head.

  • all the forming tendons associated with branchiomeric and eye muscles are of neural crest origin

PMID 19198652

Analysis of early human neural crest development

Dev Biol. 2010 Aug 15;344(2):578-92. Epub 2010 May 15.

Betters E, Liu Y, Kjaeldgaard A, Sundström E, García-Castro MI. Source Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA.


The outstanding migration and differentiation capacities of neural crest cells (NCCs) have fascinated scientists since Wilhelm His described this cell population in 1868. Today, after intense research using vertebrate model organisms, we have gained considerable knowledge regarding the origin, migration and differentiation of NCCs. However, our understanding of NCC development in human embryos remains largely uncharacterized, despite the role the neural crest plays in several human pathologies. Here, we report for the first time the expression of a battery of molecular markers before, during, or following NCC migration in human embryos from Carnegie Stages (CS) 12 to 18. Our work demonstrates the expression of Sox9, Sox10 and Pax3 transcription factors in premigratory NCCs, while actively migrating NCCs display the additional transcription factors Pax7 and AP-2alpha. Importantly, while HNK-1 labels few migrating NCCs, p75(NTR) labels a large proportion of this population. However, the broad expression of p75(NTR) - and other markers - beyond the neural crest stresses the need for the identification of additional markers to improve our capacity to investigate human NCC development, and to enable the generation of better diagnostic and therapeutic tools.

Copyright 2010 Elsevier Inc. All rights reserved.

PMID 20478300