SNW1 is a critical regulator of spatial BMP activity, neural plate border formation, and neural crest specification in vertebrate embryos
| Autor: | Caroline S. Hill, Mary Y. Wu, Michael Howell, Marie-Christine Ramel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Embryo
Nonmammalian Xenopus Ectoderm Xenopus Proteins Bioinformatics Cell Biology/Cell Signaling Developmental Biology/Pattern Formation Developmental Biology/Molecular Development 0302 clinical medicine Neural crest formation Biology (General) Zebrafish Developmental Biology/Embryology 0303 health sciences Neural Plate Developmental Biology/Morphogenesis and Cell Biology General Neuroscience Neural crest Embryo 11 Medical And Health Sciences Cell biology medicine.anatomical_structure Neural Crest Bone Morphogenetic Proteins embryonic structures Synopsis General Agricultural and Biological Sciences Neural plate Signal Transduction Research Article animal structures QH301-705.5 Embryonic Development Biology Bone morphogenetic protein General Biochemistry Genetics and Molecular Biology Protein–protein interaction 03 medical and health sciences Bmp signaling medicine Animals Cell Biology/Gene Expression 030304 developmental biology Body Patterning Neural fold General Immunology and Microbiology Gastrulation Bone Morphogenetic Protein Receptors 06 Biological Sciences Zebrafish Proteins biology.organism_classification Embryonic stem cell Molecular biology Neurulation Mesoderm formation Developmental Biology/Cell Differentiation 07 Agricultural And Veterinary Sciences Carrier Proteins 030217 neurology & neurosurgery Developmental Biology Transcription Factors |
| Zdroj: | PLoS Biology, Vol 9, Iss 2, p e1000593 (2011) PLoS Biology PLoS Biology, Vol 9, Iss 2, p e1001018 (2011) e1000593 |
| ISSN: | 1545-7885 1544-9173 |
| Popis: | In frog and fish embryos, SNW1 is a protein required for the spatio-temporal activity of BMP signaling necessary for neural plate border formation and specification of neural crest tissue. Bone morphogenetic protein (BMP) gradients provide positional information to direct cell fate specification, such as patterning of the vertebrate ectoderm into neural, neural crest, and epidermal tissues, with precise borders segregating these domains. However, little is known about how BMP activity is regulated spatially and temporally during vertebrate development to contribute to embryonic patterning, and more specifically to neural crest formation. Through a large-scale in vivo functional screen in Xenopus for neural crest fate, we identified an essential regulator of BMP activity, SNW1. SNW1 is a nuclear protein known to regulate gene expression. Using antisense morpholinos to deplete SNW1 protein in both Xenopus and zebrafish embryos, we demonstrate that dorsally expressed SNW1 is required for neural crest specification, and this is independent of mesoderm formation and gastrulation morphogenetic movements. By exploiting a combination of immunostaining for phosphorylated Smad1 in Xenopus embryos and a BMP-dependent reporter transgenic zebrafish line, we show that SNW1 regulates a specific domain of BMP activity in the dorsal ectoderm at the neural plate border at post-gastrula stages. We use double in situ hybridizations and immunofluorescence to show how this domain of BMP activity is spatially positioned relative to the neural crest domain and that of SNW1 expression. Further in vivo and in vitro assays using cell culture and tissue explants allow us to conclude that SNW1 acts upstream of the BMP receptors. Finally, we show that the requirement of SNW1 for neural crest specification is through its ability to regulate BMP activity, as we demonstrate that targeted overexpression of BMP to the neural plate border is sufficient to restore neural crest formation in Xenopus SNW1 morphants. We conclude that through its ability to regulate a specific domain of BMP activity in the vertebrate embryo, SNW1 is a critical regulator of neural plate border formation and thus neural crest specification. Author Summary A subset of cells in the ectoderm of vertebrate embryos becomes the neural crest, which contributes to the bones and cartilage of the adult face. The neural crest arises in a location between the epidermis, which becomes the future skin, and the neural plate, which becomes the future central nervous system. Through our studies in both frog and fish embryos, we have discovered that the protein SNW-domain containing protein 1 (SNW1) is absolutely essential for defining the edge of the neural plate, where neural crest forms. SNW-domain containing proteins have been implicated in a variety of nuclear activities ranging from transcriptional regulation and elongation to RNA splicing. We show that SNW1 functions upstream of bone morphogenetic protein (BMP) receptors to regulate BMP activity, and is necessary for the activity of the BMP signaling pathway at the neural plate border where the neural crest is specified. In the absence of SNW1, BMP activity is reduced in this region and neural crest cells are lost. Given that SNW1 family proteins are highly conserved from nematodes to humans, SNW1's BMP regulatory function is likely conserved in other animals. |
| Databáze: | OpenAIRE |
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