Cellular organization and boundary formation in craniofacial development

Kindberg, Abigail A.; Bush, Jeffrey O.

doi:10.1002/dvg.23271

Cited by 16 publications

(13 citation statements)

References 169 publications

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“…We demonstrate that MES cells do not migrate as a sheet, but instead exhibit fascinating and unique patterns of epithelial cell movement, prompting several fundamental questions: 1) How are initial holes in the MES established? This does not require apoptosis, but could instead involve mesenchymal cells pushing through the MES or in a cell-sorting-like behavior driven by differences in cell adhesion or actomyosin contractility between epithelial and mesenchymal cells (Kindberg and Bush, 2019;Lough et al, 2017). Matrix metalloproteinases are induced by TGFβ3 in the MES and required for secondary palate fusion (Blavier et al, 2001), suggesting a role in the initiation of MES breakage.…”

Section: Discussionmentioning

confidence: 99%

A unique form of collective epithelial migration is crucial for tissue fusion in the secondary palate and can overcome loss of epithelial apoptosis

Teng

Kaartinen

et al. 2021

Preprint

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Tissue fusion is an oft-employed process in morphogenesis which often requires the removal of the epithelia intervening multiple distinct primordia to form one continuous structure. In the mammalian secondary palate, a midline epithelial seam (MES) forms between two palatal shelves and must be removed to allow mesenchymal confluence. Abundant apoptosis and cell extrusion in this epithelial seam support their importance in its removal. However, by genetically disrupting the intrinsic apoptotic regulators BAX and BAK within the MES, we find a complete loss of cell death and cell extrusion, but successful removal of the MES, indicating that developmental compensation enables fusion. Novel static and live imaging approaches reveal that the MES is removed through a unique form of collective epithelial cell migration in which epithelial trails and islands stream through the mesenchyme to reach the oral and nasal epithelial surfaces. These epithelial trails and islands begin to express periderm markers while retaining expression of the basal epithelial marker ΔNp63, suggesting their migration to the oral and nasal surface is concomitant with their differentiation to an epithelial intermediate. Live imaging reveals anisotropic actomyosin contractility within epithelial trails that drives their peristaltic movement, and genetic loss of non-muscle myosin IIA-mediated actomyosin contractility results in dispersion of epithelial collectives and dramatic failure of normal MES migration. These findings demonstrate redundancy between cellular mechanisms of morphogenesis and reveal a crucial role for a unique form of collective epithelial migration during tissue fusion.

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Section: Discussionmentioning

confidence: 99%

A unique form of collective epithelial migration is crucial for tissue fusion in the secondary palate and can overcome loss of epithelial apoptosis

Teng

Kaartinen

et al. 2021

Preprint

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“…Indeed, the introduction of WGS in the molecular diagnostics of FDs requires advanced in silico and functional analyses, which are both necessary for the interpretation and proving of pathogenicity of genomic alterations ( Smedley et al, 2016 ; Bodea et al, 2018 ; Posey, 2019 ). The proportion of molecularly undiagnosed patients, however, clearly suggests that some of the genetic lesions, causative for FDs, lie within non-coding DNA, and could be picked up only by WGS ( Kindberg and Bush, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Targeted Next-Generation Sequencing in the Diagnosis of Facial Dysostoses

et al. 2020

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Background Defects in the development of the first and second pharyngeal arches and their derivatives result in abnormal formation of the craniofacial complex, consequently giving rise to facial dysostoses (FDs). FDs represent a group of rare and highly heterogeneous disease entities that encompass mandibulofacial dysostoses (MFDs) with normal extremities and acrofacial dysostoses (AFDs) with limb anomalies in addition to craniofacial defects. Methods We examined 11 families with variable clinical symptoms of FDs, in most of which only one member was affected. We applied two custom gene panels—first comprising 37 genes related to the genetic disorders of craniofacial development such as FDs (On-Demand AmpliSeq Thermo Fisher Scientific gene panel with two primer pools) and second composed of 61 genes and 11 single nucleotide variants (SNVs) known to be involved in the development of skull malformations, mainly in the form of craniosynostoses (SureSelect Agilent Technologies). Targeted next-generation sequencing (NGS) was performed using the Ion Torrent S5 platform. To confirm the presence of each detected variant, we have analyzed a genomic region of interest using Sanger sequencing. Results In this paper, we summarized the results of custom targeted gene panel sequencing in the cohort of sixteen patients from 11 consecutive families affected by distinct forms of FDs. We have found three novel pathogenic variants in the TCOF1 gene—c.2145_2148dupAAAG p.(Ser717Lys fs ∗ 42), c.4370delA p.(Lys1457Arg fs ∗ 118), c.83G>C p.(Arg28Pro) causing Treacher Collins syndrome type 1, two novel missense variants in the EFTUD2 gene–c.491A>G p.(Asp164Gly) and c.779T>A p.(Ile260Asn) in two female patients affected by acrofacial dysostosis Guion-Almeida type, one previously reported–c.403C>T (p.Arg135Cys), as well as one novel missense variant–c.128C>T p.(Pro43Leu) in the DHODH gene in the male patient with Miller syndrome and finally one known pathogenic variant c.574G>T p.(Glu192 ∗ ) in the SF3B4 gene in the patient with Nager syndrome. Conclusion Our study confirms the efficiency and clinical utility of the targeted gene panel sequencing and shows that this strategy is suitable and efficient in the molecular screening of variable forms of FDs.

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“…In addition to cell mixing in the suture mesenchyme, loss of Twist1 widens Msx2 expression distribution and osteogenic differentiation [ 10 , 90 , 114 ]. Loss of Twist1 also reduces the levels of ephrin receptor EphA4 and ephrin ligands ephrin-A2 ( Efna2) and ephrin-A4 ( Efna4 ), all of which are components of the eph/ephrin signaling pathway that is crucial for tissue boundary formation in vertebrates [ 10 , 85 , 171 ]. Reduced dosage of Msx2 in Twist1 +/− mice can rescue the coronal suture boundary defect to a wild type pattern [ 10 ].…”

Section: Mechanisms Underlying Coronal Craniosynostosismentioning

confidence: 99%

Cranial Neural Crest Cells and Their Role in the Pathogenesis of Craniofacial Anomalies and Coronal Craniosynostosis

Siismets

Hatch

2020

JDB

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Craniofacial anomalies are among the most common of birth defects. The pathogenesis of craniofacial anomalies frequently involves defects in the migration, proliferation, and fate of neural crest cells destined for the craniofacial skeleton. Genetic mutations causing deficient cranial neural crest migration and proliferation can result in Treacher Collins syndrome, Pierre Robin sequence, and cleft palate. Defects in post-migratory neural crest cells can result in pre- or post-ossification defects in the developing craniofacial skeleton and craniosynostosis (premature fusion of cranial bones/cranial sutures). The coronal suture is the most frequently fused suture in craniosynostosis syndromes. It exists as a biological boundary between the neural crest-derived frontal bone and paraxial mesoderm-derived parietal bone. The objective of this review is to frame our current understanding of neural crest cells in craniofacial development, craniofacial anomalies, and the pathogenesis of coronal craniosynostosis. We will also discuss novel approaches for advancing our knowledge and developing prevention and/or treatment strategies for craniofacial tissue regeneration and craniosynostosis.

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Cellular organization and boundary formation in craniofacial development

Cited by 16 publications

References 169 publications

A unique form of collective epithelial migration is crucial for tissue fusion in the secondary palate and can overcome loss of epithelial apoptosis

A unique form of collective epithelial migration is crucial for tissue fusion in the secondary palate and can overcome loss of epithelial apoptosis

Targeted Next-Generation Sequencing in the Diagnosis of Facial Dysostoses

Cranial Neural Crest Cells and Their Role in the Pathogenesis of Craniofacial Anomalies and Coronal Craniosynostosis

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