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<PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Manual"><PMID Version="1">23307071</PMID><DateCompleted><Year>2013</Year><Month>11</Month><Day>04</Day></DateCompleted><DateRevised><Year>2024</Year><Month>05</Month><Day>25</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1420-9071</ISSN><JournalIssue CitedMedium="Internet"><Volume>70</Volume><Issue>18</Issue><PubDate><Year>2013</Year><Month>Sep</Month></PubDate></JournalIssue><Title>Cellular and molecular life sciences : CMLS</Title><ISOAbbreviation>Cell Mol Life Sci</ISOAbbreviation></Journal><ArticleTitle>Novel mechanisms that pattern and shape the midbrain-hindbrain boundary.</ArticleTitle><Pagination><StartPage>3365</StartPage><EndPage>3374</EndPage><MedlinePgn>3365-74</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s00018-012-1240-x</ELocationID><Abstract><AbstractText>The midbrain-hindbrain boundary (MHB) is a highly conserved vertebrate signalling centre, acting to pattern and establish neural identities within the brain. While the core signalling pathways regulating MHB formation have been well defined, novel genetic and mechanistic processes that interact with these core components are being uncovered, helping to further elucidate the complicated networks governing MHB specification, patterning and shaping. Although formation of the MHB organiser is traditionally thought of as comprising three stages, namely positioning, induction and maintenance, we propose that a fourth stage, morphogenesis, should be considered as an additional stage in MHB formation. This review will examine evidence for novel factors regulating the first three stages of MHB development and will explore the evidence for regulation of MHB morphogenesis by non-classical MHB-patterning genes.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Dworkin</LastName><ForeName>Sebastian</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Medicine, Monash University Central Clinical School, Melbourne, VIC, 3004, Australia. sebastian.dworkin@monash.edu</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jane</LastName><ForeName>Stephen M</ForeName><Initials>SM</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2013</Year><Month>01</Month><Day>10</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Cell Mol Life Sci</MedlineTA><NlmUniqueID>9705402</NlmUniqueID><ISSNLinking>1420-682X</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019521" MajorTopicYN="N">Body Patterning</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018507" MajorTopicYN="Y">Gene Expression Regulation, Developmental</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008636" MajorTopicYN="N">Mesencephalon</DescriptorName><QualifierName UI="Q000033" MajorTopicYN="Y">anatomy &amp; histology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008959" MajorTopicYN="N">Models, Neurological</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009024" MajorTopicYN="N">Morphogenesis</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012249" MajorTopicYN="N">Rhombencephalon</DescriptorName><QualifierName UI="Q000033" MajorTopicYN="Y">anatomy &amp; histology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015027" MajorTopicYN="N">Zebrafish</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2012</Year><Month>9</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2012</Year><Month>12</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2012</Year><Month>11</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>1</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2013</Year><Month>1</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2013</Year><Month>11</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2013</Year><Month>1</Month><Day>10</Day></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">23307071</ArticleId><ArticleId IdType="pmc">PMC11113640</ArticleId><ArticleId IdType="doi">10.1007/s00018-012-1240-x</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Hirth F. On the origin and evolution of the tripartite brain. Brain Behav Evol. 2010;76(1):3&#x2013;10. doi: 10.1159/000320218.</Citation><ArticleIdList><ArticleId IdType="doi">10.1159/000320218</ArticleId><ArticleId IdType="pubmed">20926853</ArticleId></ArticleIdList></Reference><Reference><Citation>Lowery LA, Sive H. Totally tubular: the mystery behind function and origin of the brain ventricular system. BioEssays: news and reviews in molecular, cellular and developmental biology. 2009;31(4):446&#x2013;458. doi: 10.1002/bies.200800207.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/bies.200800207</ArticleId><ArticleId IdType="pmc">PMC3003255</ArticleId><ArticleId IdType="pubmed">19274662</ArticleId></ArticleIdList></Reference><Reference><Citation>Echelard Y, et al. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell. 1993;75(7):1417&#x2013;1430. doi: 10.1016/0092-8674(93)90627-3.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/0092-8674(93)90627-3</ArticleId><ArticleId IdType="pubmed">7916661</ArticleId></ArticleIdList></Reference><Reference><Citation>Lee KJ, Jessell TM. The specification of dorsal cell fates in the vertebrate central nervous system. Ann Rev Neurosci. 1999;22:261&#x2013;294. doi: 10.1146/annurev.neuro.22.1.261.</Citation><ArticleIdList><ArticleId IdType="doi">10.1146/annurev.neuro.22.1.261</ArticleId><ArticleId IdType="pubmed">10202540</ArticleId></ArticleIdList></Reference><Reference><Citation>Marin F, Puelles L. Patterning of the embryonic avian midbrain after experimental inversions: a polarizing activity from the isthmus. Dev Biol. 1994;163(1):19&#x2013;37. doi: 10.1006/dbio.1994.1120.</Citation><ArticleIdList><ArticleId IdType="doi">10.1006/dbio.1994.1120</ArticleId><ArticleId IdType="pubmed">8174775</ArticleId></ArticleIdList></Reference><Reference><Citation>Martinez S, et al. Induction of ectopic engrailed expression and fate change in avian rhombomeres: intersegmental boundaries as barriers. Mech Dev. 1995;51(2&#x2013;3):289&#x2013;303. doi: 10.1016/0925-4773(95)00376-2.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/0925-4773(95)00376-2</ArticleId><ArticleId IdType="pubmed">7547475</ArticleId></ArticleIdList></Reference><Reference><Citation>Martinez S, Wassef M, Alvarado-Mallart RM. Induction of a mesencephalic phenotype in the 2-day-old chick prosencephalon is preceded by the early expression of the homeobox gene en. Neuron. 1991;6(6):971&#x2013;981. doi: 10.1016/0896-6273(91)90237-T.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/0896-6273(91)90237-T</ArticleId><ArticleId IdType="pubmed">1675863</ArticleId></ArticleIdList></Reference><Reference><Citation>Alvarado-Mallart RM. The chick/quail transplantation model: discovery of the isthmic organizer center, brain research. Brain Res Rev. 2005;49(2):109&#x2013;113. doi: 10.1016/j.brainresrev.2005.03.001.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.brainresrev.2005.03.001</ArticleId><ArticleId IdType="pubmed">16111542</ArticleId></ArticleIdList></Reference><Reference><Citation>Rhinn M, Brand M. The midbrain&#x2013;hindbrain boundary organizer. Curr Opinion Neurobiol. 2001;11(1):34&#x2013;42. doi: 10.1016/S0959-4388(00)00171-9.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0959-4388(00)00171-9</ArticleId><ArticleId IdType="pubmed">11179870</ArticleId></ArticleIdList></Reference><Reference><Citation>Joyner AL, Liu A, Millet S. Otx2, Gbx2 and Fgf8 interact to position and maintain a mid-hindbrain organizer. Curr Opin Cell Biol. 2000;12(6):736&#x2013;741. doi: 10.1016/S0955-0674(00)00161-7.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0955-0674(00)00161-7</ArticleId><ArticleId IdType="pubmed">11063941</ArticleId></ArticleIdList></Reference><Reference><Citation>Broccoli V, Boncinelli E, Wurst W. The caudal limit of Otx2 expression positions the isthmic organizer. Nature. 1999;401(6749):164&#x2013;168. doi: 10.1038/43670.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/43670</ArticleId><ArticleId IdType="pubmed">10490025</ArticleId></ArticleIdList></Reference><Reference><Citation>Simeone A. Positioning the isthmic organizer where Otx2 and Gbx2meet. Trends Genetics : TIG. 2000;16(6):237&#x2013;240. doi: 10.1016/S0168-9525(00)02000-X.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0168-9525(00)02000-X</ArticleId><ArticleId IdType="pubmed">10827447</ArticleId></ArticleIdList></Reference><Reference><Citation>Brand M, et al. Mutations in zebrafish genes affecting the formation of the boundary between midbrain and hindbrain. Development. 1996;123:179&#x2013;190.</Citation><ArticleIdList><ArticleId IdType="pubmed">9007239</ArticleId></ArticleIdList></Reference><Reference><Citation>Picker A, et al. A novel positive transcriptional feedback loop in midbrain&#x2013;hindbrain boundary development is revealed through analysis of the zebrafish pax2.1 promoter in transgenic lines. Development. 2002;129(13):3227&#x2013;3239.</Citation><ArticleIdList><ArticleId IdType="pubmed">12070097</ArticleId></ArticleIdList></Reference><Reference><Citation>Borello U, Pierani A. Patterning the cerebral cortex: traveling with morphogens. Curr Opin Genet Dev. 2010;20(4):408&#x2013;415. doi: 10.1016/j.gde.2010.05.003.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.gde.2010.05.003</ArticleId><ArticleId IdType="pubmed">20542680</ArticleId></ArticleIdList></Reference><Reference><Citation>Wurst W, Bally-Cuif L. Neural plate patterning: upstream and downstream of the isthmic organizer. Nat Rev Neurosci. 2001;2(2):99&#x2013;108. doi: 10.1038/35053516.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/35053516</ArticleId><ArticleId IdType="pubmed">11253000</ArticleId></ArticleIdList></Reference><Reference><Citation>Hidalgo-Sanchez M, et al. Specification of the meso-isthmo-cerebellar region: the Otx2/Gbx2 boundary. Brain Res Brain Res Rev. 2005;49(2):134&#x2013;149. doi: 10.1016/j.brainresrev.2005.01.010.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.brainresrev.2005.01.010</ArticleId><ArticleId IdType="pubmed">16111544</ArticleId></ArticleIdList></Reference><Reference><Citation>Barkovich AJ, Millen KJ, Dobyns WB. A developmental and genetic classification for midbrain&#x2013;hindbrain malformations. Brain J Neurol. 2009;132(Pt 12):3199&#x2013;3230. doi: 10.1093/brain/awp247.</Citation><ArticleIdList><ArticleId IdType="doi">10.1093/brain/awp247</ArticleId><ArticleId IdType="pmc">PMC2792369</ArticleId><ArticleId IdType="pubmed">19933510</ArticleId></ArticleIdList></Reference><Reference><Citation>Wallingford JB. Planar cell polarity, ciliogenesis and neural tube defects. Hum Mol Genet. 2006;15(Spec No 2):R227&#x2013;R234.</Citation><ArticleIdList><ArticleId IdType="pubmed">16987888</ArticleId></ArticleIdList></Reference><Reference><Citation>Rhinn M, et al. Positioning of the midbrain&#x2013;hindbrain boundary organizer through global posteriorization of the neuroectoderm mediated by Wnt8 signaling. Development. 2005;132(6):1261&#x2013;1272. doi: 10.1242/dev.01685.</Citation><ArticleIdList><ArticleId IdType="doi">10.1242/dev.01685</ArticleId><ArticleId IdType="pubmed">15703279</ArticleId></ArticleIdList></Reference><Reference><Citation>Klingensmith J, et al. Neural induction and patterning in the mouse in the absence of the node and its derivatives. Dev Biol. 1999;216(2):535&#x2013;549. doi: 10.1006/dbio.1999.9525.</Citation><ArticleIdList><ArticleId IdType="doi">10.1006/dbio.1999.9525</ArticleId><ArticleId IdType="pubmed">10642791</ArticleId></ArticleIdList></Reference><Reference><Citation>Liu A, Joyner AL. EN and GBX2 play essential roles downstream of FGF8 in patterning the mouse mid/hindbrain region. Development. 2001;128(2):181&#x2013;191.</Citation><ArticleIdList><ArticleId IdType="pubmed">11124114</ArticleId></ArticleIdList></Reference><Reference><Citation>Sato T, Joyner AL. The duration of Fgf8 isthmic organizer expression is key to patterning different tectal-isthmo-cerebellum structures. Development. 2009;136(21):3617&#x2013;3626. doi: 10.1242/dev.041210.</Citation><ArticleIdList><ArticleId IdType="doi">10.1242/dev.041210</ArticleId><ArticleId IdType="pmc">PMC2761110</ArticleId><ArticleId IdType="pubmed">19793884</ArticleId></ArticleIdList></Reference><Reference><Citation>Li JY, Joyner AL. Otx2 and Gbx2 are required for refinement and not induction of mid-hindbrain gene expression. Development. 2001;128(24):4979&#x2013;4991.</Citation><ArticleIdList><ArticleId IdType="pubmed">11748135</ArticleId></ArticleIdList></Reference><Reference><Citation>Agoston Z, Schulte D. Meis2 competes with the Groucho co-repressor Tle4 for binding to Otx2 and specifies tectal fate without induction of a secondary midbrain&#x2013;hindbrain boundary organizer. Development. 2009;136(19):3311&#x2013;3322. doi: 10.1242/dev.037770.</Citation><ArticleIdList><ArticleId IdType="doi">10.1242/dev.037770</ArticleId><ArticleId IdType="pubmed">19736326</ArticleId></ArticleIdList></Reference><Reference><Citation>Jungbluth S, et al. Cell mixing between the embryonic midbrain and hindbrain. Curr Biol. 2001;11(3):204&#x2013;207. doi: 10.1016/S0960-9822(01)00049-5.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0960-9822(01)00049-5</ArticleId><ArticleId IdType="pubmed">11231158</ArticleId></ArticleIdList></Reference><Reference><Citation>Langenberg T, Brand M. Lineage restriction maintains a stable organizer cell population at the zebrafish midbrain&#x2013;hindbrain boundary. Development. 2005;132(14):3209&#x2013;3216. doi: 10.1242/dev.01862.</Citation><ArticleIdList><ArticleId IdType="doi">10.1242/dev.01862</ArticleId><ArticleId IdType="pubmed">15958515</ArticleId></ArticleIdList></Reference><Reference><Citation>Tallafuss A, Bally-Cuif L. Tracing of her5 progeny in zebrafish transgenics reveals the dynamics of midbrain&#x2013;hindbrain neurogenesis and maintenance. Development. 2003;130(18):4307&#x2013;4323. doi: 10.1242/dev.00662.</Citation><ArticleIdList><ArticleId IdType="doi">10.1242/dev.00662</ArticleId><ArticleId IdType="pubmed">12900448</ArticleId></ArticleIdList></Reference><Reference><Citation>Tossell K, et al. Lrrn1 is required for formation of the midbrain&#x2013;hindbrain boundary and organiser through regulation of affinity differences between midbrain and hindbrain cells in chick. Dev Biol. 2011;352(2):341&#x2013;352. doi: 10.1016/j.ydbio.2011.02.002.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.ydbio.2011.02.002</ArticleId><ArticleId IdType="pmc">PMC3084456</ArticleId><ArticleId IdType="pubmed">21315708</ArticleId></ArticleIdList></Reference><Reference><Citation>Holland LZ, Short S. Gene duplication, co-option and recruitment during the origin of the vertebrate brain from the invertebrate chordate brain. Brain Behav Evol. 2008;72(2):91&#x2013;105. doi: 10.1159/000151470.</Citation><ArticleIdList><ArticleId IdType="doi">10.1159/000151470</ArticleId><ArticleId IdType="pubmed">18836256</ArticleId></ArticleIdList></Reference><Reference><Citation>Glavic A, Gomez-Skarmeta JL, Mayor R. The homeoprotein Xiro1 is required for midbrain&#x2013;hindbrain boundary formation. Development. 2002;129(7):1609&#x2013;1621.</Citation><ArticleIdList><ArticleId IdType="pubmed">11923198</ArticleId></ArticleIdList></Reference><Reference><Citation>Crossley PH, Martinez S, Martin GR. Midbrain development induced by FGF8 in the chick embryo. Nature. 1996;380(6569):66&#x2013;68. doi: 10.1038/380066a0.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/380066a0</ArticleId><ArticleId IdType="pubmed">8598907</ArticleId></ArticleIdList></Reference><Reference><Citation>Reifers F, et al. Fgf8 is mutated in zebrafish acerebellar (ace) mutants and is required for maintenance of midbrain&#x2013;hindbrain boundary development and somitogenesis. Development. 1998;125(13):2381&#x2013;2395.</Citation><ArticleIdList><ArticleId IdType="pubmed">9609821</ArticleId></ArticleIdList></Reference><Reference><Citation>Leucht C, et al. MicroRNA-9 directs late organizer activity of the midbrain&#x2013;hindbrain boundary. Nat Neurosci. 2008;11(6):641&#x2013;648. doi: 10.1038/nn.2115.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nn.2115</ArticleId><ArticleId IdType="pubmed">18454145</ArticleId></ArticleIdList></Reference><Reference><Citation>Geling A, et al. bHLH transcription factor Her5 links patterning to regional inhibition of neurogenesis at the midbrain&#x2013;hindbrain boundary. Development. 2003;130(8):1591&#x2013;1604. doi: 10.1242/dev.00375.</Citation><ArticleIdList><ArticleId IdType="doi">10.1242/dev.00375</ArticleId><ArticleId IdType="pubmed">12620984</ArticleId></ArticleIdList></Reference><Reference><Citation>Chi CL, et al. The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum. Development. 2003;130(12):2633&#x2013;2644. doi: 10.1242/dev.00487.</Citation><ArticleIdList><ArticleId IdType="doi">10.1242/dev.00487</ArticleId><ArticleId IdType="pubmed">12736208</ArticleId></ArticleIdList></Reference><Reference><Citation>Badde A, Schulte D. A role for receptor protein tyrosine phosphatase lambda in midbrain development. J Neurosci Off J Soc Neurosci. 2008;28(24):6152&#x2013;6164. doi: 10.1523/JNEUROSCI.5593-07.2008.</Citation><ArticleIdList><ArticleId IdType="doi">10.1523/JNEUROSCI.5593-07.2008</ArticleId><ArticleId IdType="pmc">PMC6670526</ArticleId><ArticleId IdType="pubmed">18550757</ArticleId></ArticleIdList></Reference><Reference><Citation>Itoh M, et al. A role for iro1 and iro7 in the establishment of an anteroposterior compartment of the ectoderm adjacent to the midbrain&#x2013;hindbrain boundary. Development. 2002;129(10):2317&#x2013;2327.</Citation><ArticleIdList><ArticleId IdType="pubmed">11973265</ArticleId></ArticleIdList></Reference><Reference><Citation>Tossell K, et al. Notch signalling stabilises boundary formation at the midbrain&#x2013;hindbrain organiser. Development. 2011;138(17):3745&#x2013;3757. doi: 10.1242/dev.070318.</Citation><ArticleIdList><ArticleId IdType="doi">10.1242/dev.070318</ArticleId><ArticleId IdType="pmc">PMC3152928</ArticleId><ArticleId IdType="pubmed">21795283</ArticleId></ArticleIdList></Reference><Reference><Citation>Sugiyama S, Funahashi J, Nakamura H. Antagonizing activity of chick Grg4 against tectum-organizing activity. Dev Biol. 2000;221(1):168&#x2013;180. doi: 10.1006/dbio.2000.9643.</Citation><ArticleIdList><ArticleId IdType="doi">10.1006/dbio.2000.9643</ArticleId><ArticleId IdType="pubmed">10772799</ArticleId></ArticleIdList></Reference><Reference><Citation>Shinga J, et al. Early patterning of the prospective midbrain&#x2013;hindbrain boundary by the HES-related gene XHR1 in Xenopus embryos. Mech Dev. 2001;109(2):225&#x2013;239. doi: 10.1016/S0925-4773(01)00528-7.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0925-4773(01)00528-7</ArticleId><ArticleId IdType="pubmed">11731236</ArticleId></ArticleIdList></Reference><Reference><Citation>Canning CA, et al. Sustained interactive Wnt and FGF signaling is required to maintain isthmic identity. Dev Biol. 2007;305(1):276&#x2013;286. doi: 10.1016/j.ydbio.2007.02.009.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.ydbio.2007.02.009</ArticleId><ArticleId IdType="pubmed">17383629</ArticleId></ArticleIdList></Reference><Reference><Citation>Wittmann DM, et al. Spatial analysis of expression patterns predicts genetic interactions at the mid-hindbrain boundary. PLoS Comput Biol. 2009;5(11):e1000569. doi: 10.1371/journal.pcbi.1000569.</Citation><ArticleIdList><ArticleId IdType="doi">10.1371/journal.pcbi.1000569</ArticleId><ArticleId IdType="pmc">PMC2774268</ArticleId><ArticleId IdType="pubmed">19936059</ArticleId></ArticleIdList></Reference><Reference><Citation>Dworkin S, et al. Midbrain&#x2013;hindbrain boundary patterning and morphogenesis are regulated by diverse grainy head-like 2-dependent pathways. Development. 2012;139(3):525&#x2013;536. doi: 10.1242/dev.066522.</Citation><ArticleIdList><ArticleId IdType="doi">10.1242/dev.066522</ArticleId><ArticleId IdType="pubmed">22223680</ArticleId></ArticleIdList></Reference><Reference><Citation>Nakamura H, Sato T, Suzuki-Hirano A. Isthmus organizer for mesencephalon and metencephalon. Dev Growth Differ. 2008;50(Suppl 1):S113&#x2013;S118. doi: 10.1111/j.1440-169X.2008.00995.x.</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/j.1440-169X.2008.00995.x</ArticleId><ArticleId IdType="pubmed">18494704</ArticleId></ArticleIdList></Reference><Reference><Citation>Suzuki-Hirano A, Sato T, Nakamura H. Regulation of isthmic Fgf8 signal by sprouty2. Development. 2005;132(2):257&#x2013;265. doi: 10.1242/dev.01581.</Citation><ArticleIdList><ArticleId IdType="doi">10.1242/dev.01581</ArticleId><ArticleId IdType="pubmed">15590739</ArticleId></ArticleIdList></Reference><Reference><Citation>Kim M, McGinnis W. Phosphorylation of Grainy head by ERK is essential for wound-dependent regeneration but not for development of an epidermal barrier. Proc Nat Acad Sci USA. 2011;108(2):650&#x2013;655. doi: 10.1073/pnas.1016386108.</Citation><ArticleIdList><ArticleId IdType="doi">10.1073/pnas.1016386108</ArticleId><ArticleId IdType="pmc">PMC3021071</ArticleId><ArticleId IdType="pubmed">21187384</ArticleId></ArticleIdList></Reference><Reference><Citation>Buckles GR, et al. Combinatorial Wnt control of zebrafish midbrain&#x2013;hindbrain boundary formation. Mech Dev. 2004;121(5):437&#x2013;447. doi: 10.1016/j.mod.2004.03.026.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.mod.2004.03.026</ArticleId><ArticleId IdType="pubmed">15147762</ArticleId></ArticleIdList></Reference><Reference><Citation>Adams KA, et al. The transcription factor Lmx1b maintains Wnt1 expression within the isthmic organizer. Development. 2000;127(9):1857&#x2013;1867.</Citation><ArticleIdList><ArticleId IdType="pubmed">10751174</ArticleId></ArticleIdList></Reference><Reference><Citation>O&#x2019;Hara FP, et al. Zebrafish Lmx1b.1 and Lmx1b.2 are required for maintenance of the isthmic organizer. Development. 2005;132(14):3163&#x2013;3173. doi: 10.1242/dev.01898.</Citation><ArticleIdList><ArticleId IdType="doi">10.1242/dev.01898</ArticleId><ArticleId IdType="pmc">PMC1361118</ArticleId><ArticleId IdType="pubmed">15944182</ArticleId></ArticleIdList></Reference><Reference><Citation>Guo C, et al. Lmx1b is essential for Fgf8 and Wnt1 expression in the isthmic organizer during tectum and cerebellum development in mice. Development. 2007;134(2):317&#x2013;325. doi: 10.1242/dev.02745.</Citation><ArticleIdList><ArticleId IdType="doi">10.1242/dev.02745</ArticleId><ArticleId IdType="pubmed">17166916</ArticleId></ArticleIdList></Reference><Reference><Citation>Erickson T, et al. Pbx proteins cooperate with Engrailed to pattern the midbrain&#x2013;hindbrain and diencephalic-mesencephalic boundaries. Developmental biology. 2007;301(2):504&#x2013;517. doi: 10.1016/j.ydbio.2006.08.022.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.ydbio.2006.08.022</ArticleId><ArticleId IdType="pmc">PMC1850147</ArticleId><ArticleId IdType="pubmed">16959235</ArticleId></ArticleIdList></Reference><Reference><Citation>Koike S, et al. Autotaxin is required for the cranial neural tube closure and establishment of the midbrain&#x2013;hindbrain boundary during mouse development. Dev Dyn Off Publ Am Assoc Anat. 2011;240(2):413&#x2013;421.</Citation><ArticleIdList><ArticleId IdType="pubmed">21246658</ArticleId></ArticleIdList></Reference><Reference><Citation>Belting HG, et al. spiel ohne grenzen/pou2 is required during establishment of the zebrafish midbrain&#x2013;hindbrain boundary organizer. Development. 2001;128(21):4165&#x2013;4176.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC4027960</ArticleId><ArticleId IdType="pubmed">11684654</ArticleId></ArticleIdList></Reference><Reference><Citation>Bouchard M, et al. Identification of Pax2-regulated genes by expression profiling of the mid-hindbrain organizer region. Development. 2005;132(11):2633&#x2013;2643. doi: 10.1242/dev.01833.</Citation><ArticleIdList><ArticleId IdType="doi">10.1242/dev.01833</ArticleId><ArticleId IdType="pubmed">15872005</ArticleId></ArticleIdList></Reference><Reference><Citation>Xu J, Liu Z, Ornitz DM. Temporal and spatial gradients of Fgf8 and Fgf17 regulate proliferation and differentiation of midline cerebellar structures. Development. 2000;127(9):1833&#x2013;1843.</Citation><ArticleIdList><ArticleId IdType="pubmed">10751172</ArticleId></ArticleIdList></Reference><Reference><Citation>Xu FX, Chye ML. Expression of cysteine proteinase during developmental events associated with programmed cell death in brinjal. Plant J Cell Mol Biol. 1999;17(3):321&#x2013;327. doi: 10.1046/j.1365-313X.1999.00370.x.</Citation><ArticleIdList><ArticleId IdType="doi">10.1046/j.1365-313X.1999.00370.x</ArticleId><ArticleId IdType="pubmed">10097390</ArticleId></ArticleIdList></Reference><Reference><Citation>Panhuysen M, et al. Effects of Wnt1 signaling on proliferation in the developing mid-/hindbrain region. Mol Cell Neurosci. 2004;26(1):101&#x2013;111. doi: 10.1016/j.mcn.2004.01.011.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.mcn.2004.01.011</ArticleId><ArticleId IdType="pubmed">15121182</ArticleId></ArticleIdList></Reference><Reference><Citation>Sgado P, et al. Slow progressive degeneration of nigral dopaminergic neurons in postnatal Engrailed mutant mice. Proc Nat Acad Sci USA. 2006;103(41):15242&#x2013;15247. doi: 10.1073/pnas.0602116103.</Citation><ArticleIdList><ArticleId IdType="doi">10.1073/pnas.0602116103</ArticleId><ArticleId IdType="pmc">PMC1622807</ArticleId><ArticleId IdType="pubmed">17015829</ArticleId></ArticleIdList></Reference><Reference><Citation>Alavian KN, et al. Elevated P75NTR expression causes death of engrailed-deficient midbrain dopaminergic neurons by Erk1/2 suppression. Neural Dev. 2009;4:11. doi: 10.1186/1749-8104-4-11.</Citation><ArticleIdList><ArticleId IdType="doi">10.1186/1749-8104-4-11</ArticleId><ArticleId IdType="pmc">PMC2667502</ArticleId><ArticleId IdType="pubmed">19291307</ArticleId></ArticleIdList></Reference><Reference><Citation>Radice GL, et al. Developmental defects in mouse embryos lacking N-cadherin. Dev Biol. 1997;181(1):64&#x2013;78. doi: 10.1006/dbio.1996.8443.</Citation><ArticleIdList><ArticleId IdType="doi">10.1006/dbio.1996.8443</ArticleId><ArticleId IdType="pubmed">9015265</ArticleId></ArticleIdList></Reference><Reference><Citation>Lele Z, et al. parachute/n-cadherin is required for morphogenesis and maintained integrity of the zebrafish neural tube. Development. 2002;129(14):3281&#x2013;3294.</Citation><ArticleIdList><ArticleId IdType="pubmed">12091300</ArticleId></ArticleIdList></Reference><Reference><Citation>Dworkin S, et al. CREB activity modulates neural cell proliferation, midbrain&#x2013;hindbrain organization and patterning in zebrafish. Dev Biol. 2007;307(1):127&#x2013;141. doi: 10.1016/j.ydbio.2007.04.026.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.ydbio.2007.04.026</ArticleId><ArticleId IdType="pubmed">17531969</ArticleId></ArticleIdList></Reference><Reference><Citation>Giraldez AJ, et al. MicroRNAs regulate brain morphogenesis in zebrafish. Science. 2005;308(5723):833&#x2013;838. doi: 10.1126/science.1109020.</Citation><ArticleIdList><ArticleId IdType="doi">10.1126/science.1109020</ArticleId><ArticleId IdType="pubmed">15774722</ArticleId></ArticleIdList></Reference><Reference><Citation>Gutzman JH, et al. Formation of the zebrafish midbrain&#x2013;hindbrain boundary constriction requires laminin-dependent basal constriction. Mech Dev. 2008;125(11&#x2013;12):974&#x2013;983. doi: 10.1016/j.mod.2008.07.004.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.mod.2008.07.004</ArticleId><ArticleId IdType="pmc">PMC2780020</ArticleId><ArticleId IdType="pubmed">18682291</ArticleId></ArticleIdList></Reference><Reference><Citation>Lowery LA, Sive H. Initial formation of zebrafish brain ventricles occurs independently of circulation and requires the nagie oko and snakehead/atp1a1a.1 gene products. Development. 2005;132(9):2057&#x2013;2067. doi: 10.1242/dev.01791.</Citation><ArticleIdList><ArticleId IdType="doi">10.1242/dev.01791</ArticleId><ArticleId IdType="pubmed">15788456</ArticleId></ArticleIdList></Reference><Reference><Citation>Pirone DM, Fukuhara S, Gutkind JS, Burbelo PD. SPECs, small binding proteins for Cdc42. J Biol Chem. 2000;275(30):22650&#x2013;22656.</Citation><ArticleIdList><ArticleId IdType="pubmed">10816584</ArticleId></ArticleIdList></Reference><Reference><Citation>Ching KH, Kisailus AE, Burbelo PD. The role of SPECs, small Cdc42-binding proteins, in F-actin accumulation at the immunological synapse. J Biol Chem. 2005;280(25):23660&#x2013;23667.</Citation><ArticleIdList><ArticleId IdType="pubmed">15840583</ArticleId></ArticleIdList></Reference><Reference><Citation>Ching KH, Kisailus AE, Burbelo PD. Biochemical characterization of distinct regions of SPEC molecules and their role in phagocytosis. Exp Cell Res. 2007;313(1):10&#x2013;21.</Citation><ArticleIdList><ArticleId IdType="pubmed">17045588</ArticleId></ArticleIdList></Reference><Reference><Citation>Mullins MC, et al. Large-scale mutagenesis in the zebrafish: in search of genes controlling development in a vertebrate. Curr Biol. 1994;4(3):189&#x2013;202. doi: 10.1016/S0960-9822(00)00048-8.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0960-9822(00)00048-8</ArticleId><ArticleId IdType="pubmed">7922324</ArticleId></ArticleIdList></Reference><Reference><Citation>Kudoh T, et al. A gene expression screen in zebrafish embryogenesis. Genome Res. 2001;11(12):1979&#x2013;1987. doi: 10.1101/gr.209601.</Citation><ArticleIdList><ArticleId IdType="doi">10.1101/gr.209601</ArticleId><ArticleId IdType="pubmed">11731487</ArticleId></ArticleIdList></Reference><Reference><Citation>Thisse B, Thisse C (2004) Fast Release Clones: A High Throughput Expression Analysis. ZFIN Direct Data Submission (http://zfin.org)</Citation></Reference></ReferenceList></PubmedData></PubmedArticle></PubmedArticleSet>