Bmps and Id2a Act Upstream of Twist1 To Restrict Ectomesenchyme Potential of the Cranial Neural Crest
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{"title"=>"Bmps and Id2a act upstream of twist1 to restrict ectomesenchyme potential of the cranial neural crest", "type"=>"journal", "authors"=>[{"first_name"=>"Ankita", "last_name"=>"Das", "scopus_author_id"=>"55309114400"}, {"first_name"=>"J. Gage", "last_name"=>"Crump", "scopus_author_id"=>"7006432634"}], "year"=>2012, "source"=>"PLoS Genetics", "identifiers"=>{"scopus"=>"2-s2.0-84863649372", "sgr"=>"84863649372", "issn"=>"15537390", "doi"=>"10.1371/journal.pgen.1002710", "pmid"=>"22589745", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "pui"=>"365220728"}, "id"=>"3fb0616e-a4d5-363c-afe4-ce540f156efb", "abstract"=>"Cranial neural crest cells (CNCCs) have the remarkable capacity to generate both the non-ectomesenchyme derivatives of the peripheral nervous system and the ectomesenchyme precursors of the vertebrate head skeleton, yet how these divergent lineages are specified is not well understood. Whereas studies in mouse have indicated that the Twist1 transcription factor is important for ectomesenchyme development, its role and regulation during CNCC lineage decisions have remained unclear. Here we show that two Twist1 genes play an essential role in promoting ectomesenchyme at the expense of non-ectomesenchyme gene expression in zebrafish. Twist1 does so by promoting Fgf signaling, as well as potentially directly activating fli1a expression through a conserved ectomesenchyme-specific enhancer. We also show that Id2a restricts Twist1 activity to the ectomesenchyme lineage, with Bmp activity preferentially inducing id2a expression in non-ectomesenchyme precursors. We therefore propose that the ventral migration of CNCCs away from a source of Bmps in the dorsal ectoderm promotes ectomesenchyme development by relieving Id2a-dependent repression of Twist1 function. Together our model shows how the integration of Bmp inhibition at its origin and Fgf activation along its migratory route would confer temporal and spatial specificity to the generation of ectomesenchyme from the neural crest.", "link"=>"http://www.mendeley.com/research/bmps-id2a-act-upstream-twist1-restrict-ectomesenchyme-potential-cranial-neural-crest", "reader_count"=>36, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Student > Doctoral Student"=>6, "Researcher"=>7, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Student > Doctoral Student"=>6, "Researcher"=>7, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>27, "Medicine and Dentistry"=>3, "Neuroscience"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>27}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}}, "reader_count_by_country"=>{"Republic of Singapore"=>1, "United States"=>1, "United Kingdom"=>2, "Spain"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/641830"], "description"=>"<p>(A–L) Colorimetric in situs show ectopic <i>sox10</i> arch expression at 18 hpf and reductions of <i>dlx2a</i> and <i>fli1a</i> arch expression at 24 hpf in <i>sox10</i>:Gal4VP16; <i>UAS</i>:Bmp4 embryos but not <i>sox10</i>:Gal4VP16 control or <i>id2a</i>-MO-injected embryos. <i>sox10</i>:Gal4VP16; <i>UAS</i>:Bmp4 embryos injected with <i>id2a</i>-MO showed complete rescue of <i>sox10</i> and <i>dlx2a</i> expression and partial rescue of <i>fli1a</i> expression. Arches are numbered and arrows denote the second arch, white arrowheads the developing ear, and red arrowheads the vasculature. Scale bar = 50 µm. (M–O) Quantification of gene expression defects. The mutant index is based on the following: 0 = normal, 1 = partially defective, 2 = fully defective. Fully defective was defined as gene expression being of equal intensity to that seen in un-injected <i>sox10</i>:Gal4VP16; <i>UAS</i>:Bmp4 embryos. For <i>sox10</i>, partially defective was defined as a reduction in the number of expressing cells and/or the intensity of arch expression compared to un-injected <i>sox10</i>:Gal4VP16; <i>UAS</i>:Bmp4 embryos. For <i>fli1a</i> and <i>dlx2a</i>, partially defective was defined as a level of arch expression intermediate between un-injected <i>sox10</i>:Gal4VP16; <i>UAS</i>:Bmp4 and <i>sox10</i>:Gal4VP16 control embryos. The rescue of Bmp4 misexpression defects with <i>id2a</i>-MO injection was statistically significant for all genes based on a Tukey-Kramer HSD test (α = 0.05). Standard errors of the mean are shown.</p>", "links"=>[], "tags"=>["id2a", "rescues", "ectomesenchyme", "defects", "caused", "bmp4"], "article_id"=>312321, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Ankita Das", "J. Gage Crump"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002710.g010", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reduction_of_Id2a_rescues_the_ectomesenchyme_defects_caused_by_Bmp4_misexpression_/312321", "title"=>"Reduction of Id2a rescues the ectomesenchyme defects caused by Bmp4 misexpression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-10 00:38:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/640740"], "description"=>"<p>(A,B) <i>sox10</i>:GFP-positive and -negative cells were isolated from un-injected or <i>twist1a/1b</i>-MO embryos at 18 hpf by FACS. (C) Fold changes of the GFP+/GFP− ratios between <i>twist1a/1b</i>-MO and un-injected controls show the top 25 up-regulated (blue) and down-regulated (red) genes after Twist1 depletion. Color codes indicate where genes are expressed based on the published literature (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002710#pgen.1002710.s008\" target=\"_blank\">Table S1</a> for references). (D–O) Confocal projections of fluorescent in situ hybridizations show expanded expression of <i>gch2</i> and <i>nr4a2b</i> at 18 hpf, ectopic arch expression (arrows) of <i>sox10</i> and <i>foxd3</i> at 24 hpf, but no change in <i>sox9b</i> and <i>tfap2a</i> expression at 24 hpf in <i>twist1a/1b</i>-MO versus un-injected controls. Scale bar = 50 µm.</p>", "links"=>[], "tags"=>["profiling"], "article_id"=>311237, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Ankita Das", "J. Gage Crump"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002710.g002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_expression_profiling_in_twist1a_1b_MO_embryos_/311237", "title"=>"Gene expression profiling in <i>twist1a/1b</i>-MO embryos.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-10 00:20:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/641541"], "description"=>"<p>(A–D) Whole mount in situs at 18 hpf show ectopic expression of <i>sox10</i> in the arches (numbered) of <i>sox10</i>:Gal4VP16; <i>UAS</i>:Bmp4; <i>UAS</i>:mKR embryos (n = 8/8) compared to <i>sox10</i>:Gal4VP16; <i>UAS</i>:mKR controls (n = 0/8) and reductions of <i>dlx2a</i> in <i>sox10</i>:Gal4VP16; <i>UAS</i>:Bmp4; <i>UAS</i>:mKR embryos (n = 4/4) compared to <i>sox10</i>:Gal4VP16; <i>UAS</i>:mKR controls (n = 0/4). Arrows indicate the second arch and white arrowheads the developing ear. (E–H) Double fluorescent in situs for <i>mKR</i> (red) and <i>fli1a</i> or <i>dlx2a</i> (green) at 24 hpf show reduction of <i>fli1a</i> arch expression in <i>sox10</i>:Gal4VP16; <i>UAS</i>:Bmp4; <i>UAS</i>:mKR embryos (n = 5/5) compared to <i>sox10</i>:Gal4VP16; <i>UAS</i>:mKR controls (n = 0/9) and reduction of <i>dlx2a</i> arch expression in <i>sox10</i>:Gal4VP16; <i>UAS</i>:Bmp4; <i>UAS</i>:mKR embryos (n = 4/4) compared to <i>sox10</i>:Gal4VP16; <i>UAS</i>:mKR controls (n = 0/3). The mKR transgene was included as a lineage tracer for CNCC-derived cells that migrated into the arches. (I,J) Skeletal staining at 5 dpf shows severe loss of craniofacial skeleton in <i>sox10</i>:Gal4VP16; <i>UAS</i>:Bmp4; <i>UAS</i>:mKR embryos (n = 7/7) compared to <i>sox10</i>:Gal4VP16; <i>UAS</i>:mKR controls (n = 0/9). (K,L) In situs for <i>foxd3</i> at 48 hpf reveal largely normal patterns of glia in <i>sox10</i>:Gal4VP16; <i>UAS</i>:Bmp4; <i>UAS</i>:mKR embryos (n = 8) and <i>sox10</i>:Gal4VP16; <i>UAS</i>:mKR controls (n = 11). (M–P) In situs at 28 hpf show normal <i>dct</i>-positive melanophore precursors in <i>sox10</i>:Gal4VP16; <i>UAS</i>:Bmp4; <i>UAS</i>:mKR embryos (n = 12) and <i>sox10</i>:Gal4VP16; <i>UAS</i>:mKR controls (n = 15) and normal <i>xdh</i>-positive xanthophore precursors in <i>sox10</i>:Gal4VP16; <i>UAS</i>:Bmp4; <i>UAS</i>:mKR embryos (n = 10) and <i>sox10</i>:Gal4VP16; <i>UAS</i>:mKR controls (n = 10). Scale bars = 50 µm.</p>", "links"=>[], "tags"=>["bmp4", "migrating", "cnccs", "inhibits", "ectomesenchyme"], "article_id"=>312041, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Ankita Das", "J. Gage Crump"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002710.g008", "stats"=>{"downloads"=>3, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Misexpression_of_Bmp4_in_migrating_CNCCs_inhibits_ectomesenchyme_formation_/312041", "title"=>"Misexpression of Bmp4 in migrating CNCCs inhibits ectomesenchyme formation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-10 00:34:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/641292"], "description"=>"<p>(A–F) Whole mount in situs show ectopic arch expression of <i>sox10</i> at 18 hpf in <i>sox10</i>:Gal4VP16; <i>UAS</i>:Id2a embryos (n = 7/7) but not <i>sox10</i>:Gal4VP16 only controls (n = 0/9), loss of <i>fli1a</i> arch expression at 24 hpf in <i>sox10</i>:Gal4VP16; <i>UAS</i>:Id2a embryos (n = 4/4) but not <i>sox10</i>:Gal4VP16 only controls (n = 0/17), and mild reductions of <i>dlx2a</i> arch expression at 18 hpf in <i>sox10</i>:Gal4VP16; <i>UAS</i>:Id2a embryos (n = 5/5) but not <i>sox10</i>:Gal4VP16 only controls (n = 0/8). Arches are numbered. Arrows denote the second arch, white arrowheads the developing ear, and red arrowheads the vasculature. (G and H) Skeletal staining at 5 dpf shows severe reduction of the craniofacial skeleton in <i>sox10</i>:Gal4VP16; <i>UAS</i>:Id2a embryos (n = 17/17) compared to <i>sox10</i>:Gal4VP16 only controls (n = 0/22). (I and J) In situs for <i>dct</i> expression at 28 hpf show that melanophore precursors are unaffected in <i>sox10</i>:Gal4VP16; <i>UAS</i>:Id2a embryos (n = 8) and <i>sox10</i>:Gal4VP16 only controls (n = 8). (K and L) In situs for <i>xdh</i> expression at 28 hpf show that xanthophore precursors are unaffected in <i>sox10</i>:Gal4VP16; <i>UAS</i>:Id2a embryos (n = 4) and <i>sox10</i>:Gal4VP16 only controls (n = 4). (M–P) <i>twist1a</i> expression at 18 hpf is unaffected in <i>sox10</i>:Gal4VP16; <i>UAS</i>:Id2a embryos (n = 12) versus <i>sox10</i>:Gal4VP16 only controls (n = 11). <i>twist1b</i> expression at 18 hpf is similarly unaffected in <i>sox10</i>:Gal4VP16; <i>UAS</i>:Id2a embryos (n = 7) versus <i>sox10</i>:Gal4VP16 controls (n = 8). Id2a misexpression embryos are to the right in I–P. Scale bars = 50 µm.</p>", "links"=>[], "tags"=>["id2a", "cnccs", "inhibits", "ectomesenchyme"], "article_id"=>311786, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Ankita Das", "J. Gage Crump"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002710.g006", "stats"=>{"downloads"=>2, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Forced_expression_of_Id2a_in_CNCCs_inhibits_ectomesenchyme_specification_/311786", "title"=>"Forced expression of Id2a in CNCCs inhibits ectomesenchyme specification.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-10 00:29:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/641417"], "description"=>"<p>(A) Confocal projection of pSMAD1/5/8 immunostaining at 12 hpf shows that all <i>sox10</i>:GFP-positive CNCCs display high pSMAD1/5/8. (B–D) At 16.5 hpf, a projection (B) and a high-magnification section (C, boxed area in B) show that pSMAD1/5/8 remains high in the dorsal non-ectomesenchyme but is lower in the more ventral ectomesenchyme. An orthogonal section (D, taken at the level of the line in C) shows that high pSMAD1/5/8 CNCCs remain in the neural epithelium whereas low pSMAD1/5/8 CNCCs are positioned more medial and ventral. The eye also displays high pSMAD1/5/8. Abbreviations: D, dorsal; V, ventral; A, anterior; P, posterior; M, medial; L, lateral; m, mandibular arch ectomesenchyme; h, hyoid arch ectomesenchyme; n, non-ectomesenchyme; e, ectomesenchyme; ve, ventral epithelium. Scale bar = 50 µm.</p>", "links"=>[], "tags"=>["selectively", "down-regulated", "ectomesenchyme"], "article_id"=>311916, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Ankita Das", "J. Gage Crump"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002710.g007", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bmp_activity_is_selectively_down_regulated_in_ectomesenchyme_precursors_/311916", "title"=>"Bmp activity is selectively down-regulated in ectomesenchyme precursors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-10 00:31:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/641138"], "description"=>"<p>(A–C) Colorimetric in situs show weak expression of <i>id2a</i> in pre-migratory CNCCs at 12 hpf (dorsal view with anterior up, arrows indicate bilateral CNCC fields) and increasing expression in non-ectomesenchyme precursors at 17.5 and 19 hpf (lateral views). (D–I) Confocal projections of fluorescent in situs show co-localization of <i>id2a</i> with <i>sox10</i> in CNCCs at 12 hpf (D) and 14 hpf (E), as well as co-localization in the non-ectomesenchyme at 16.5 hpf (F). At 16.5 hpf, <i>id2a</i> is excluded from ectomesenchyme CNCCs marked by <i>dlx2a</i> (G) and <i>twist1a</i> (H), with <i>twist1a</i> also being expressed in head mesoderm. In <i>sox10:</i>Gal4VP16; <i>UAS</i>:Bmp4 embryos, <i>id2a</i> and <i>sox10</i> are expressed ectopically in the ectomesenchyme (white arrows). Arrowheads indicate otic expression of <i>sox10</i>. Scale bars = 50 µm.</p>", "links"=>[], "tags"=>["regulated", "bmps", "excluded"], "article_id"=>311632, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Ankita Das", "J. Gage Crump"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002710.g005", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_id2a_is_regulated_by_Bmps_and_excluded_from_the_ectomesenchyme_/311632", "title"=>"<i>id2a</i> is regulated by Bmps and excluded from the ectomesenchyme.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-10 00:27:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/641937"], "description"=>"<p>At 12 hpf, Bmps in the neural plate border ectoderm promote moderate expression of <i>id2a</i> in multipotent CNCCs. As ectomesenchyme precursors delaminate from the neuroepithelium and migrate away from the Bmp source (16 hpf), they downregulate <i>id2a</i> expression, which allows Twist1 to induce <i>fli1a</i> expression and potentiate Fgf signaling. Fgf signaling then inhibits <i>sox10</i> and promotes <i>dlx2a</i> expression. In the non-ectomesenchyme, sustained Bmp activity and <i>id2a</i> expression dampens Twist1-dependent inhibition of neural, glia, and pigment gene expression programs. Lateral diagrams are shown on the left and cross-sectional diagrams on the right.</p>", "links"=>[], "tags"=>["ectomesenchyme"], "article_id"=>312434, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Ankita Das", "J. Gage Crump"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002710.g011", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Model_of_ectomesenchyme_specification_/312434", "title"=>"Model of ectomesenchyme specification.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-10 00:40:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/330667", "https://ndownloader.figshare.com/files/330701", "https://ndownloader.figshare.com/files/330747", "https://ndownloader.figshare.com/files/330777", "https://ndownloader.figshare.com/files/330840", "https://ndownloader.figshare.com/files/330875", "https://ndownloader.figshare.com/files/330906", "https://ndownloader.figshare.com/files/330940"], "description"=>"<div><p>Cranial neural crest cells (CNCCs) have the remarkable capacity to generate both the non-ectomesenchyme derivatives of the peripheral nervous system and the ectomesenchyme precursors of the vertebrate head skeleton, yet how these divergent lineages are specified is not well understood. Whereas studies in mouse have indicated that the Twist1 transcription factor is important for ectomesenchyme development, its role and regulation during CNCC lineage decisions have remained unclear. Here we show that two Twist1 genes play an essential role in promoting ectomesenchyme at the expense of non-ectomesenchyme gene expression in zebrafish. Twist1 does so by promoting Fgf signaling, as well as potentially directly activating <em>fli1a</em> expression through a conserved ectomesenchyme-specific enhancer. We also show that Id2a restricts Twist1 activity to the ectomesenchyme lineage, with Bmp activity preferentially inducing <em>id2a</em> expression in non-ectomesenchyme precursors. We therefore propose that the ventral migration of CNCCs away from a source of Bmps in the dorsal ectoderm promotes ectomesenchyme development by relieving Id2a-dependent repression of Twist1 function. Together our model shows how the integration of Bmp inhibition at its origin and Fgf activation along its migratory route would confer temporal and spatial specificity to the generation of ectomesenchyme from the neural crest.</p> </div>", "links"=>[], "tags"=>["bmps", "id2a", "upstream", "twist1", "ectomesenchyme", "cranial", "neural", "crest"], "article_id"=>125299, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Ankita Das", "J. Gage Crump"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002710.s001", "https://dx.doi.org/10.1371/journal.pgen.1002710.s002", "https://dx.doi.org/10.1371/journal.pgen.1002710.s003", "https://dx.doi.org/10.1371/journal.pgen.1002710.s004", "https://dx.doi.org/10.1371/journal.pgen.1002710.s005", "https://dx.doi.org/10.1371/journal.pgen.1002710.s006", "https://dx.doi.org/10.1371/journal.pgen.1002710.s007", "https://dx.doi.org/10.1371/journal.pgen.1002710.s008"], "stats"=>{"downloads"=>24, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Bmps_and_Id2a_Act_Upstream_of_Twist1_To_Restrict_Ectomesenchyme_Potential_of_the_Cranial_Neural_Crest/125299", "title"=>"Bmps and Id2a Act Upstream of Twist1 To Restrict Ectomesenchyme Potential of the Cranial Neural Crest", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-05-10 01:28:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/641722"], "description"=>"<p>(A–D) In situs at 12 hpf show loss of axial <i>ntl</i> and mesodermal <i>myod</i> expression in Antivin-mRNA-injected embryos compared to un-injected controls. (E,F) Confocal projections of <i>her5</i>:GFP expression at 19 hpf show loss of pouch endoderm (arrows) but not brain (arrowheads) in Antivin-mRNA-injected embryos compared to un-injected controls. (G,H) In situs at 15.5 hpf show normal ectomesenchyme induction of <i>dlx2a</i> in Antivin-mRNA-injected embryos (n = 12) and un-injected controls (n = 13). Arches are numbered. (I,J) Double fluorescent in situs at 15.5 hpf show normal induction of <i>dlx2a</i> (green) in <i>sox10</i>-positive CNCCs (red, yellow indicates co-localization) in Antivin-mRNA-injected embryos (n = 15) and un-injected controls (n = 9). (K,L) Double fluorescent in situs at 19 hpf show complementary expression of <i>fli1a</i> (green) in ectomesenchyme and <i>sox10</i> (red) in non-ectomesenchyme in Antivin-mRNA-injected embryos (n = 5) and un-injected controls (n = 8). Scale bar = 50 µm.</p>", "links"=>[], "tags"=>["endoderm", "ectomesenchyme"], "article_id"=>312215, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Ankita Das", "J. Gage Crump"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002710.g009", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mesoderm_and_endoderm_are_not_essential_for_ectomesenchyme_formation_/312215", "title"=>"Mesoderm and endoderm are not essential for ectomesenchyme formation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-10 00:36:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/640859"], "description"=>"<p>(A,B) In situs at 18 hpf show that expression of the Fgf target gene <i>pea3</i> is reduced in the arches (numbered) of <i>twist1a/1b</i>-MO embryos (n = 8/8) compared to un-injected controls (n = 0/12). (C–L) <i>sox10</i>:Gal4VP16; <i>UAS</i>:dnFgfr1a embryos show ectopic arch expression of <i>sox10</i> at 18 hpf (n = 8/8) versus controls (n = 0/8), reduction of <i>dlx2a</i> at 24 hpf (n = 3/3) versus controls (n = 0/3), but no change in <i>fli1a</i> at 24 hpf (n = 0/7) versus controls (n = 0/5). <i>twist1a</i> expression was unchanged at 24 hpf in dnFgfr1a embryos (n = 10) compared to controls (n = 7), as was <i>twist1b</i> expression in dnFgfr1a embryos (n = 8) compared to controls (n = 8). Black arrows indicate the second arch, white arrowheads the ear, and red arrowheads the vasculature. Scale bar = 50 µm.</p>", "links"=>[], "tags"=>["signaling", "depends", "twist1", "regulates", "subset", "ectomesenchyme"], "article_id"=>311353, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Ankita Das", "J. Gage Crump"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002710.g003", "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Fgf_signaling_depends_on_Twist1_and_regulates_a_subset_of_ectomesenchyme_gene_expression_/311353", "title"=>"Fgf signaling depends on Twist1 and regulates a subset of ectomesenchyme gene expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-10 00:22:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/641018"], "description"=>"<p>(A) Schematic shows the <i>fli1a</i> genomic locus with hatch marks at 1 kb intervals. Predicted enhancers (grey boxes, “A–H”) and the first exon (red box) are shown. Below are the various enhancer constructs analyzed, with the <i>hsp70I</i> core promoter in blue and GFP in green. Wild-type (black) and mutant (red) versions of the putative Twist1 binding site are also shown, as is the percentage of transient transgenic embryos showing GFP expression in the pharyngeal arches or vasculature. (B) Alignment of the central portion of the F enhancer between five fish species and mouse. The putative bHLH/Twist1 binding site is boxed in red. (C,D) Confocal projections of 32 hpf <i>sox10</i>:dsRed embryos injected at the one-cell-stage with <i>fli1a</i>-F enhancer constructs. The wild-type (C) but not mutant (D) enhancer drives arch expression. (E and F) Confocal sections of merged GFP and DIC channels show that a stable <i>Tg(fli1a-F-hsp70I:GFP)</i> line displays arch GFP expression in 32 hpf wild-type (E) but not <i>twist1a/1b</i>-MO (F) embryos. (G) Luciferase activity relative to renilla firefly activity in 293T cells transfected with wild-type or mutant <i>fli1a</i>-F enhancer reporter constructs, with or without a Twist1 expression plasmid. Asterisks indicate significant comparisons using a student's t-test (p<0.05). Arbitrary units and standard error of the mean are shown.</p>", "links"=>[], "tags"=>["regulates", "ectomesenchyme-specific"], "article_id"=>311514, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Ankita Das", "J. Gage Crump"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002710.g004", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Twist1_regulates_fli1a_expression_through_an_ectomesenchyme_specific_enhancer_/311514", "title"=>"Twist1 regulates <i>fli1a</i> expression through an ectomesenchyme-specific enhancer.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-10 00:25:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/640547"], "description"=>"<p>(A–D) Whole mount in situ hybridizations of <i>sox10</i> expression at 18 hpf show ectopic expression in the arches (numbered and second arch indicated by black arrow) of <i>twist1a/1b</i>-MO (n = 16/16) and <i>sox10</i>:Gal4VP16; <i>UAS</i>:dnTwist1b (n = 4/4) embryos compared to un-injected (n = 0/14) and <i>sox10</i>:Gal4VP16 only (n = 0/9) controls. White arrowheads indicate otic expression. (E–H) Whole mount in situs at 24 hpf show reduction of <i>fli1a</i> expression in the arch ectomesenchyme (numbered) of <i>twist1a/1b</i>-MO (n = 12/12) and <i>sox10</i>:Gal4VP16; <i>UAS</i>:dnTwist1b (n = 5/5) embryos compared to un-injected (n = 0/13) and <i>sox10</i>:Gal4VP16 only (n = 0/8) controls. Insets in E and F highlight arch ectomesenchyme which is reduced in <i>twist1a/1b</i>-MO embryos. Vascular expression of <i>fli1a</i> (red arrowheads) is unaffected. (I–L) Whole mount in situs at 18 hpf show a slight reduction of <i>dlx2a</i> in <i>sox10</i>:Gal4VP16; <i>UAS</i>:dnTwist1b embryos (n = 4/4) but not un-injected (n = 0/6), <i>twist1a/1b</i>-MO (n = 0/8), and <i>sox10</i>:Gal4VP16 only (n = 0/6) embryos. (M-P) Skeletal staining at 5 dpf shows severe loss of CNCC-derived head skeleton in <i>twist1a/1b</i>-MO embryos (n = 21/21) and primarily jaw reductions in <i>sox10</i>:Gal4VP16; <i>UAS</i>:dnTwist1b embryos (n = 9/9) compared to no defects in un-injected (n = 0/24) and <i>sox10</i>:Gal4VP16 only (n = 0/16) controls. Whereas only small remnants remain of the CNCC-derived skeleton (arrows), the mesoderm-derived otic capsule cartilage (arrowheads) and posterior neurocranium are less affected in <i>twist1a/1b</i>-MO embryos. (Q–T) In situs for <i>dct</i> expression at 28 hpf show normal melanophore precursors in un-injected (n = 14), <i>twist1a/1b</i>-MO (n = 12), <i>sox10</i>:Gal4VP16 only (n = 8), and <i>sox10</i>:Gal4VP16; <i>UAS</i>:dnTwist1b (n = 8) embryos. (U–X) In situs for <i>xdh</i> expression at 28 hpf show normal xanthophore precursors in un-injected (n = 7), <i>twist1a/1b</i>-MO (n = 5), <i>sox10</i>:Gal4VP16 only (n = 9), and <i>sox10</i>:Gal4VP16; <i>UAS</i>:dnTwist1b (n = 8) embryos. (Y-AB) In situs for <i>foxd3</i> expression at 48 hpf reveal largely normal patterns of glia in un-injected (n = 9), <i>twist1a/1b</i>-MO (n = 8), <i>sox10</i>:Gal4VP16 only (n = 9), and <i>sox10</i>:Gal4VP16; <i>UAS</i>:dnTwist1b (n = 8) embryos. Scale bar = 50 µm.</p>", "links"=>[], "tags"=>["genes", "ectomesenchyme", "specification"], "article_id"=>311035, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Ankita Das", "J. Gage Crump"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002710.g001", "stats"=>{"downloads"=>3, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Twist1_genes_are_required_for_ectomesenchyme_specification_in_zebrafish_/311035", "title"=>"Twist1 genes are required for ectomesenchyme specification in zebrafish.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-10 00:17:15"}

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Relative Metric

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