Foxc2CreERT2 knock‐in mice mark stage‐specific Foxc2‐expressing cells during mouse organogenesis

Amin, Mohammed Badrul; Miura, Naoyuki; Uddin, Mohammad Khaja Mafij; Islam, Mohammod Johirul; Yoshida, Nobuaki; Iseki, Sachiko; Kume, Tsutomu; Trainor, Paul A.; Saitsu, Hirotomo; Aoto, Kazushi

doi:10.1111/cga.12198

Cited by 8 publications

(21 citation statements)

References 34 publications

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“…Foxc2 gene, which is necessary for mesenchymal-epithelial interactions during craniofacial development [ 25 – 27 ], has been detected in mesodermal and neural crest derivatives [ 28 ]. As a mesenchymal tissue derived from neural crest, the dental apical papilla also expressed Foxc2 [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Foxc2 and BMP2 Induce Osteogenic/Odontogenic Differentiation and Mineralization of Human Stem Cells from Apical Papilla

Wen

Zhang

et al. 2018

Stem Cells International

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As a transcription factor regulated by bone morphogenetic protein 2 (BMP2), Forkhead c2 (Foxc2) plays a pivot role in osteogenesis/odontogenesis. However, the role of Foxc2 and BMP2 in regulating osteo-/odontogenic differentiation and mineralization of stem cells from apical papilla (SCAP) is still uncertain. In this research, overexpression of Foxc2 gene significantly improved the proliferation of SCAP four days and eight days after transfection, but overexpression of both Foxc2 and BMP2 genes significantly inhibited the proliferation of SCAP eight days after transfection. RT-qPCR and western blot results indicated that SCAP-Foxc2-BMP2 significantly upregulated osteo-/odontogenic genes and proteins at most of the time points in SCAP after transfection. Moreover, SCAP-Foxc2-BMP2 formed notably more alkaline phosphatase-positive and alizarin red-positive mineralized nodules than other three group cells sixteen days after transfection. In conclusion, our findings revealed that Foxc2 and BMP2 synergistically promoted osteo-/odontogenic differentiation and mineralization of SCAP in vitro.

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Section: Discussionmentioning

confidence: 99%

Foxc2 and BMP2 Induce Osteogenic/Odontogenic Differentiation and Mineralization of Human Stem Cells from Apical Papilla

Wen

Zhang

et al. 2018

Stem Cells International

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“…Taken together with data from previous studies, our results indicate that Foxc2 is expressed in both the neural crest derived cells of pharyngeal arches 2–6 and the endothelium of the pharyngeal arch arteries. Furthermore, our recent lineage tracing analyses demonstrate that these Foxc2 positive progenitor cells provide a considerable source of mesenchymal and endothelial cells to the aorta, pulmonary trunk, valves, and endocardial cushions during cardiac morphogenesis (Amin et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…Foxc2 is expressed in migrating cardiac neural crest cells, and in the outflow tract endothelium (Fig. ) (Amin et al, ). Therefore, we initially examined whether Foxc2 loss‐of‐function disrupted cardiac neural crest cell migration in association with the observed cardiac phenotypes.…”

Section: Resultsmentioning

confidence: 99%

“…Defects in outflow tract septation may be due to perturbation of the migration and/or differentiation of cardiac neural crest cells, or due to a disruption in development of the outflow tract endothelium with which cardiac neural crest cells interact. Foxc2 is expressed in migrating cardiac neural crest cells, and in the outflow tract (Amin et al, 2017). Therefore, we initially examined whether Foxc2 loss-of-function disrupted cardiac neural crest cell migration in association with the observed cardiac phenotypes.…”

Section: Abnormal Cardiac Neural Crest Cell Migration and Contributiomentioning

confidence: 99%

“…The forkhead box transcription factor C2 (Foxc2) is expressed during embryonic development in the presomitic and paraxial mesoderm (Miura et al, 1993;Winnier et al, 1997), in the endothelium of the pharyngeal arch arteries, outflow tract, and ventricles, and in cardiac neural crest cells that colonize the pharyngeal arches and outflow tract (Iida et al, 1997;Winnier et al, 1999;Seo et al, 2006). More recently, our lineage tracing analyses of Foxc2 expressing cardiac neural crest cells revealed that these cells additionally contribute to the aorta, pulmonary trunk, valves, and endocardial cushions (Amin et al, 2017). Furthermore, studies in mice have indicated that Foxc2 is expressed in, and plays a critical role in proper development of lymphatic vessels and valves (Dagenais et al, 2004;Petrova et al, 2004;Seo et al, 2006;Sabine et al, 2012), and consistent with these observations, heterozygous mutations in FOXC2 are associated with congenital lymphedema distichiasis in humans (Sutkowska et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Foxc2 is required for proper cardiac neural crest cell migration, outflow tract septation, and ventricle expansion

Inman

Caiaffa

Melton

et al. 2018

Developmental Dynamics

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Background: Proper development of the great vessels of the heart, and septation of the cardiac outflow tract requires cardiac neural crest cells. These cells give rise to the parasympathetic cardiac ganglia, the smooth muscle layer of the great vessels, some cardiomyocytes and the conotruncal cushions and aorticopulmonary septum of the outflow tract. Ablation of cardiac neural crest cells results in defective patterning of each of these structures. Previous studies have shown that targeted deletion of the forkhead transcription factor C2 (Foxc2), results in cardiac phenotypes similar to that derived from cardiac neural crest cell ablation. Results: We report that Foxc2−/− embryos on the 129s6/SvEv inbred genetic background display persistent truncus arteriosus and hypoplastic ventricles prior to embryonic lethality. Foxc2 loss-of-function resulted in perturbed cardiac neural crest cell migration and their reduced contribution to the outflow tract as evidenced by lineage tracing analyses together with perturbed expression of the neural crest cell markers Sox10 and Crabp1. Foxc2 loss-of-function also resulted in alterations in PlexinD1, Twist1, PECAM1 and Hand1/2 expression in association with vascular and ventricular defects. Conclusions: Our data indicate Foxc2 is required for proper migration of cardiac neural crest cells, septation of the outflow tract, and development of the ventricles.

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Cell lineage‐ and expression‐based inference of the roles of forkhead box transcription factor Foxc2 in craniofacial development

Takenoshita

Takechi

Hoang

et al. 2021

Developmental Dynamics

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Background Foxc2 is a member of the winged helix/forkhead (Fox) box family of transcription factors. Loss of function of Foxc2 causes craniofacial abnormalities such as cleft palate and deformed cranial base, but its role during craniofacial development remains to be elucidated. Results The contributions of Foxc2‐positive and its descendant cells to the craniofacial structure at E18.5 were examined using a tamoxifen‐inducible Cre driver mouse (Foxc2‐CreERT2) crossed with the R26R‐LacZ reporter mouse. Foxc2 expression at E8.5 is restricted to the cranial mesenchyme, contributing to specific components including the cranial base, sensory capsule, tongue, upper incisor, and middle ear. Expression at E10.5 was still positively regulated in most of those regions. In situ hybridization analysis of Foxc2 and its closely related gene, Foxc1, revealed that expression domains of these genes largely overlap in the cephalic mesenchyme. Meanwhile, the tongue expressed Foxc2 but not Foxc1, and its development was affected by the neural crest‐specific deletion of Foxc2 in mice (Wnt1‐Cre; Foxc2fl/fl). Conclusions Foxc2 is expressed in cranial mesenchyme that contributes to specific craniofacial tissue components from an early stage, and it seems to be involved in their development in cooperation with Foxc1. Foxc2 also has its own role in tongue development.

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Foxc2^CreERT2 knock‐in mice mark stage‐specific Foxc2‐expressing cells during mouse organogenesis

Cited by 8 publications

References 34 publications

Foxc2 and BMP2 Induce Osteogenic/Odontogenic Differentiation and Mineralization of Human Stem Cells from Apical Papilla

Foxc2 and BMP2 Induce Osteogenic/Odontogenic Differentiation and Mineralization of Human Stem Cells from Apical Papilla

Foxc2 is required for proper cardiac neural crest cell migration, outflow tract septation, and ventricle expansion

Cell lineage‐ and expression‐based inference of the roles of forkhead box transcription factor Foxc2 in craniofacial development

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