The roof plate boundary is a bi-directional organiser of dorsal neural tube and choroid plexus development

The roof plate is a signalling centre positioned at the dorsal midline of the central nervous system and generates dorsalising morphogenic signals along the length of the neuraxis. Within cranial ventricles, the roof plate gives rise to choroid plexus, which regulates the internal environment of the developing and adult brain and spinal cord via the secretion of cerebrospinal fluid. Using the fourth ventricle as our model, we show that the organiser properties of the roof plate are determined by its boundaries with the adjacent neuroepithelium. Through a combination of in ovo transplantation, co-culture and electroporation techniques in chick embryos between embryonic days 3 and 6, we demonstrate that organiser properties are maintained by interactions between the non-neural roof plate and the neural rhombic lip. At the molecular level, this interaction is mediated by Delta-Notch signalling and upregulation of the chick homologue of Hes1: chairy2. Gain- and loss-of-function approaches reveal that cdelta1 is both necessary and sufficient for organiser function. Our results also demonstrate that while chairy2 is specifically required for the maintenance of the organiser, its ectopic expression is not sufficient to recapitulate organiser properties. Expression of atonal1 in the rhombic lip adjacent at the roof plate boundary is acutely dependent on both boundary cell interactions and Delta-Notch signalling. Correspondingly, the roof plate boundary organiser also signals to the roof plate itself to specify the expression of early choroid plexus markers. Thus, the roof plate boundary organiser signals bi-directionally to acutely coordinate the development of adjacent neural and non-neural tissues.

[1]  C. Irving,et al.  Notch signalling stabilises boundary formation at the midbrain-hindbrain organiser , 2011, Development.

[2]  Maria K. Lehtinen,et al.  The Cerebrospinal Fluid Provides a Proliferative Niche for Neural Progenitor Cells , 2011, Neuron.

[3]  T. Pierfelice,et al.  Notch in the Vertebrate Nervous System: An Old Dog with New Tricks , 2011, Neuron.

[4]  M. K. Cooper,et al.  Transventricular delivery of Sonic hedgehog is essential to cerebellar ventricular zone development , 2010, Proceedings of the National Academy of Sciences.

[5]  S. Dymecki,et al.  Sonic hedgehog is required for vascular outgrowth in the hindbrain choroid plexus. , 2010, Developmental biology.

[6]  H. Zoghbi,et al.  Math1 Is Essential for the Development of Hindbrain Neurons Critical for Perinatal Breathing , 2009, Neuron.

[7]  S. Dey,et al.  Sonic hedgehog signaling regulates a novel epithelial progenitor domain of the hindbrain choroid plexus , 2009, Development.

[8]  Ryoichiro Kageyama,et al.  Dynamic Notch signaling in neural progenitor cells and a revised view of lateral inhibition , 2008, Nature Neuroscience.

[9]  D. Balciunas,et al.  Development and Notch Signaling Requirements of the Zebrafish Choroid Plexus , 2008, PloS one.

[10]  V. Korzh,et al.  In vivo Analysis of Choroid Plexus Morphogenesis in Zebrafish , 2008, PloS one.

[11]  T. Ohtsuka,et al.  Hes genes and neurogenin regulate non-neural versus neural fate specification in the dorsal telencephalic midline , 2008, Development.

[12]  A. Sherman,et al.  Localised axial progenitor cell populations in the avian tail bud are not committed to a posterior Hox identity , 2008, Development.

[13]  Jane E. Johnson Faculty Opinions recommendation of Oscillations in notch signaling regulate maintenance of neural progenitors. , 2008 .

[14]  Ryoichiro Kageyama,et al.  Oscillations in Notch Signaling Regulate Maintenance of Neural Progenitors , 2008, Neuron.

[15]  S. Liddelow,et al.  The blood–CSF barrier explained: when development is not immaturity , 2008, BioEssays : news and reviews in molecular, cellular and developmental biology.

[16]  L. Wilson,et al.  Retinoic acid is a potential dorsalising signal in the late embryonic chick hindbrain , 2007, BMC Developmental Biology.

[17]  S. Takada,et al.  Wnt canonical pathway restricts graded Shh/Gli patterning activity through the regulation of Gli3 expression , 2007, Development.

[18]  D. Chambers,et al.  Tissue interactions in the developing chick diencephalon , 2007, Neural Development.

[19]  S. Dymecki,et al.  Molecularly and temporally separable lineages form the hindbrain roof plate and contribute differentially to the choroid plexus , 2007, Development.

[20]  Ryoichiro Kageyama,et al.  The Hes gene family: repressors and oscillators that orchestrate embryogenesis , 2007, Development.

[21]  L. Wilson,et al.  Temporal identity transition in the avian cerebellar rhombic lip. , 2006, Developmental biology.

[22]  K. Millen,et al.  The roof plate regulates cerebellar cell-type specification and proliferation , 2006, Development.

[23]  Ryoichiro Kageyama,et al.  Persistent and high levels of Hes1 expression regulate boundary formation in the developing central nervous system , 2006, Development.

[24]  R. Awatramani,et al.  Hindbrain Rhombic Lip Is Comprised of Discrete Progenitor Cell Populations Allocated by Pax6 , 2005, Neuron.

[25]  Yanzhen Cui Hairy is a cell context signal controlling Notch activity , 2005, Development, growth & differentiation.

[26]  H. Zoghbi,et al.  Math1 Expression Redefines the Rhombic Lip Derivatives and Reveals Novel Lineages within the Brainstem and Cerebellum , 2005, Neuron.

[27]  Gord Fishell,et al.  Math1 Is Expressed in Temporally Discrete Pools of Cerebellar Rhombic-Lip Neural Progenitors , 2005, Neuron.

[28]  Ching-mei Hsu,et al.  Direct and indirect roles of CNS dorsal midline cells in choroid plexus epithelia formation , 2005, Development.

[29]  Michael Brand,et al.  Lineage restriction maintains a stable organizer cell population at the zebrafish midbrain-hindbrain boundary , 2005, Development.

[30]  A. Lumsden,et al.  Compartments and their boundaries in vertebrate brain development , 2005, Nature Reviews Neuroscience.

[31]  K. Millen,et al.  Roof plate-dependent patterning of the vertebrate dorsal central nervous system. , 2005, Developmental biology.

[32]  A. Tallafuss,et al.  Inhibition of neurogenesis at the zebrafish midbrain-hindbrain boundary by the combined and dose-dependent activity of a new hairy/E(spl) gene pair , 2004, Development.

[33]  A. Lumsden,et al.  Hedgehog signaling from the ZLI regulates diencephalic regional identity , 2004, Nature Neuroscience.

[34]  L. Niswander,et al.  Coordinate regulation of neural tube patterning and proliferation by TGFbeta and WNT activity. , 2004, Developmental biology.

[35]  K. Millen,et al.  Mechanisms of roof plate formation in the vertebrate CNS , 2004, Nature Reviews Neuroscience.

[36]  A. Joyner,et al.  Cell Behaviors and Genetic Lineages of the Mesencephalon and Rhombomere 1 , 2004, Neuron.

[37]  M. Maden,et al.  Generating gradients of retinoic acid in the chick embryo: Cyp26C1 expression and a comparative analysis of the Cyp26 enzymes , 2004, Developmental dynamics : an official publication of the American Association of Anatomists.

[38]  C. Plessy,et al.  Her5 acts as a prepattern factor that blocks neurogenin1 and coe2 expression upstream of Notch to inhibit neurogenesis at the midbrain-hindbrain boundary , 2004, Development.

[39]  D. Ish-Horowicz,et al.  Notch activity is required to maintain floorplate identity and to control neurogenesis in the chick hindbrain and spinal cord. , 2003, The International journal of developmental biology.

[40]  J. Y. Kuwada,et al.  bHLH transcription factor Her5 links patterning to regional inhibition of neurogenesis at the midbrain-hindbrain boundary , 2003, Development.

[41]  Charlotte I. Wang,et al.  BMP signaling patterns the dorsal and intermediate neural tube via regulation of homeobox and helix-loop-helix transcription factors. , 2002, Development.

[42]  H. Kondoh,et al.  Wnt signaling plays an essential role in neuronal specification of the dorsal spinal cord. , 2002, Genes & development.

[43]  K. Tomita,et al.  Hes1 and Hes3 regulate maintenance of the isthmic organizer and development of the mid/hindbrain , 2001, The EMBO journal.

[44]  A. Lumsden,et al.  Boundary Formation and Compartition in the Avian Diencephalon , 2001, The Journal of Neuroscience.

[45]  A. Lumsden,et al.  A new developmental compartment in the forebrain regulated by Lunatic fringe , 2001, Nature Neuroscience.

[46]  J. Briscoe,et al.  Specification of neuronal fates in the ventral neural tube , 2001, Current Opinion in Neurobiology.

[47]  M. Wassef,et al.  Ectopic engrailed 1 expression in the dorsal midline causes cell death, abnormal differentiation of circumventricular organs and errors in axonal pathfinding. , 2000, Development.

[48]  G. Weinmaster,et al.  Fringe differentially modulates Jagged1 and Delta1 signalling through Notch1 and Notch2 , 2000, Nature Cell Biology.

[49]  O. Pourquié,et al.  Notch signalling is required for cyclic expression of the hairy-like gene HES1 in the presomitic mesoderm. , 2000, Development.

[50]  T. Jessell,et al.  Genetic ablation reveals that the roof plate is essential for dorsal interneuron specification , 2000, Nature.

[51]  M. Hatten,et al.  The role of the rhombic lip in avian cerebellum development. , 1999, Development.

[52]  C. Irving,et al.  Regeneration of isthmic tissue is the result of a specific and direct interaction between rhombomere 1 and midbrain. , 1999, Development.

[53]  T. Ohtsuka,et al.  Hes1 and Hes5 as Notch effectors in mammalian neuronal differentiation , 1999, The EMBO journal.

[54]  T. Jessell,et al.  Neuronal patterning by BMPs: a requirement for GDF7 in the generation of a discrete class of commissural interneurons in the mouse spinal cord. , 1998, Genes & development.

[55]  T. Jessell,et al.  A Role for the Roof Plate and Its Resident TGFβ-Related Proteins in Neuronal Patterning in the Dorsal Spinal Cord , 1997, Cell.

[56]  Olivier Pourquié,et al.  Maintenance of neuroepithelial progenitor cells by Delta–Notch signalling in the embryonic chick retina , 1997, Current Biology.

[57]  M. Hatten,et al.  Embryonic Precursor Cells from the Rhombic Lip Are Specified to a Cerebellar Granule Neuron Identity , 1996, Neuron.

[58]  U. Dräger,et al.  Influence of the choroid plexus on cerebellar development: analysis of retinoic acid synthesis. , 1996, Brain research. Developmental brain research.

[59]  J. Lewis,et al.  A chick homologue of Serrate and its relationship with Notch and Delta homologues during central neurogenesis. , 1996, Developmental biology.

[60]  Y. Jan,et al.  Delta is a ventral to dorsal signal complementary to Serrate, another Notch ligand, in Drosophila wing formation. , 1996, Genes & development.

[61]  F. Díaz-Benjumea,et al.  Serrate signals through Notch to establish a Wingless-dependent organizer at the dorsal/ventral compartment boundary of the Drosophila wing. , 1995, Development.

[62]  S. Blair,et al.  Notch regulates wingless expression and is not required for reception of the paracrine wingless signal during wing margin neurogenesis in Drosophila. , 1995, Development.

[63]  David Ish-Horowicz,et al.  Expression of a Delta homologue in prospective neurons in the chick , 1995, Nature.

[64]  A. Garcı́a-Bellido,et al.  Roles of the Notch gene in Drosophila wing morphogenesis , 1994, Mechanisms of Development.

[65]  M. Lawrence,et al.  Isolation, characterization, cDNA cloning and gene expression of an avian transthyretin. Implications for the evolution of structure and function of transthyretin in vertebrates. , 1991, European journal of biochemistry.

[66]  B. Christ,et al.  An experimental and ultrastructural study on the development of the avian choroid plexus , 1989, Cell and Tissue Research.

[67]  V. Krizhanovsky,et al.  A novel role for the choroid plexus in BMP-mediated inhibition of differentiation of cerebellar neural progenitors , 2006, Mechanisms of Development.

[68]  J. Duncan,et al.  The choroid plexus-cerebrospinal fluid system: from development to aging. , 2005, Current topics in developmental biology.

[69]  A. Joyner,et al.  Early mesencephalon/metencephalon patterning and development of the cerebellum. , 1997, Perspectives on developmental neurobiology.

[70]  M. Dziadek,et al.  Capacity to form choroid plexus-like cells in vitro is restricted to specific regions of the mouse neural ectoderm. , 1993, Development.

[71]  G. Morriss-Kay Retinoids in normal development and teratogenesis , 1992 .

[72]  G. Dohrmann,et al.  The choroid plexus of the mouse: a macroscopic, microscopic and fine structural study. , 1970, Zeitschrift fur mikroskopisch-anatomische Forschung.

[73]  Herdson Pb,et al.  The choroid plexus of the mouse: a macroscopic, microscopic and fine structural study. , 1970 .

[74]  C. Plessy,et al.  Summary Her 5 acts as a prepattern factor that blocks neurogenin 1 and coe 2 expression upstream of Notch to inhibit neurogenesis at the midbrain-hindbrain boundary , 2022 .