Cell cycle arrest in node cells governs ciliogenesis at the node to break left-right symmetry

Komatsu, Yoshihiro; Kaartinen, Vesa; Mishina, Yuji

doi:10.1242/dev.068833

Cited by 29 publications

(30 citation statements)

References 39 publications

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“…Epiblast specific loss of ACVR1/ALK2 affects the ability of ventral cells in the node to enter G 0 (Komatsu et al, 2011). Deletion of ALK2 attenuated the level of stabilized p27 Kip1 cyclin-dependent kinase inhibitor normally required to inhibit nodal cell proliferation and formation of a primary cilium.…”

Section: Discussionmentioning

confidence: 99%

BMP signaling is required for cell cleavage in preimplantation-mouse embryos

Mochel

Luong

Chiang

et al. 2015

Developmental Biology

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The mechanisms regulating cell division during development of the mouse pre-implantation embryo are poorly understood. We have investigated whether bone morphogenetic protein (BMP) signaling is involved in controlling cell cycle during mouse pre-implantation development. We mapped and quantitated the dynamic activities of BMP signaling through high-resolution immunofluorescence imaging combined with a 3D segmentation method. Immunostaining for phosphorylated Smad1/5/8 shows that BMP signaling is activated in mouse embryos as early as the 4-cell stage, and becomes spatially restricted by late blastocyst stage. Perturbation of BMP signaling in preimplantation mouse embryos, whether by treatment with a small molecule inhibitor, with Noggin protein, or by over-expression of a dominant-negative BMP receptor, indicates that BMPs regulate cell cleavage up to the morula stage. These results indicate that BMP signaling is active during mouse pre-implantation development and is required for cell cleavage in preimplantation mouse embryos.

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Section: Discussionmentioning

confidence: 99%

BMP signaling is required for cell cleavage in preimplantation-mouse embryos

Mochel

Luong

Chiang

et al. 2015

Developmental Biology

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“…FGF signaling is important for cilial length [125]. BMP signaling through ACVR1 is critical to form cilia at the node during gastrulation by negatively regulating cell cycle progression [126]. Planer Cell Polarity (PCP) signaling is a pathway critical for craniofacial development that utilizes some components of Wnt signaling pathway but is beta-catenin independent.…”

Section: Ciliopathymentioning

confidence: 99%

Neural crest cell signaling pathways critical to cranial bone development and pathology

Mishina

Snider

2014

Experimental Cell Research

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Neural crest cells appear early during embryogenesis and give rise to many structures in the mature adult. In particular, a specific population of neural crest cells migrates to and populates developing cranial tissues. The ensuing differentiation of these cells via individually complex and often intersecting signaling pathways is indispensible to growth and development of the craniofacial complex. Much research has been devoted to this area of development with particular emphasis on cell signaling events required for physiologic development. Understanding such mechanisms will allow researchers to investigate ways in which they can be exploited in order to treat a multitude of diseases affecting the craniofacial complex. Knowing how these multipotent cells are driven towards distinct fates could, in due course, allow patients to receive regenerative therapies for tissues lost to a variety of pathologies. In order to realize this goal, nucleotide sequencing advances allowing snapshots of entire genomes and exomes are being utilized to identify molecular entities associated with disease states. Once identified, these entities can be validated for biological significance with other methods. A crucial next step is the integration of knowledge gleaned from observations in disease states with normal physiology to generate an explanatory model for craniofacial development. This review seeks to provide a current view of the landscape on cell signaling and fate determination of the neural crest and to provide possible avenues of approach for future research.

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“…To prepare homozygous mutant pre-osteoblasts for Bmpr1a and Acvr1, isolated cells were treated with 100 ng/ml 4-hydroxytamoxifen for 6 days, exchanging media every other day before sorting. Cells were stained with fluorescein di β-D-galactopyranoside (FDG) and fractionated by FACS according to manufacturer's procedures for FluoReporter ® lacZ Flow Cytometry Kits (Thermo Fisher Scientific, #F-1930)(Komatsu et al, 2011). BMP2 treatment for pre-osteoblasts was done at 100ng/ml for 30 minutes (R&D, #355-BM).…”

Section: Methodsmentioning

confidence: 99%

BmpR1A is a major type 1 BMP receptor for BMP-Smad signaling during skull development

Pan

Zhang

Abraham

et al. 2017

Developmental Biology

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Craniosynostosis is caused by premature fusion of one or more sutures in an infant skull, resulting in abnormal facial features. The molecular and cellular mechanisms by which genetic mutations cause craniosynostosis are incompletely characterized, and many of the causative genes for diverse types of syndromic craniosynostosis have not yet been identified. We previously demonstrated that augmentation of BMP signaling mediated by a constitutively active BMP type IA receptor (ca-BmpR1A) in neural crest cells (ca1A hereafter) causes craniosynostosis and superimposition of heterozygous null mutation of Bmpr1a rescues premature suture fusion (ca1A;1aH hereafter). In this study, we superimposed heterozygous null mutations of the other two BMP type I receptors, Bmpr1b and Acvr1 (ca1A;1bH and ca1A;AcH respectively hereafter) to further dissect involvement of BMP-Smad signaling. Unlike caA1;1aH, ca1A;1bH and ca1A;AcH did not restore the craniosynostosis phenotypes. In our in vivo study, Smad-dependent BMP signaling was decreased to normal levels in mut;1aH mice. However, BMP receptor-regulated Smads (R-Smads; pSmad1/5/9 hereafter) levels were comparable between ca1A, ca1A;1bH and ca1A;AcH mice, and elevated compared to control mice. Bmpr1a, Bmpr1b and Acvr1 null cells were used to examine potential mechanisms underlying the differences in ability of heterozygosity for Bmpr1a vs. Bmpr1b or Acvr1 to rescue the mut phenotype. pSmad1/5/9 level was undetectable in Bmpr1a homozygous null cells while pSmad1/5/9 levels did not decrease in Bmpr1b or Acvr1 homozygous null cells. Taken together, our study indicates that different levels of expression and subsequent activation of Smad signaling differentially contribute each BMP type I receptor to BMP-Smad signaling and craniofacial development. These results also suggest differential involvement of each type 1 receptor in pathogenesis of syndromic craniosynostoses.

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Cell cycle arrest in node cells governs ciliogenesis at the node to break left-right symmetry

Cited by 29 publications

References 39 publications

BMP signaling is required for cell cleavage in preimplantation-mouse embryos

BMP signaling is required for cell cleavage in preimplantation-mouse embryos

Neural crest cell signaling pathways critical to cranial bone development and pathology

BmpR1A is a major type 1 BMP receptor for BMP-Smad signaling during skull development

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