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RESEARCH PRODUCT
NOTCH, a new signaling pathway implicated in holoprosencephaly.
Valérie DupéVéronique DavidIsabelle GicquelChristèle DubourgYann Le PétillonClaude BendavidTimothy P. BohanSandra MercierUsha KiniGeorges BourrouillouSylvie OdentChristel Thauvin-robinetLucie Rochardsubject
MaleMESH: Signal TransductionCandidate gene[SDV.GEN] Life Sciences [q-bio]/GeneticsChick EmbryoMESH: Amino Acid SequenceMESH: Base SequenceHoloprosencephalyMESH: Animals[SDV.BDD]Life Sciences [q-bio]/Development BiologyGenetics (clinical)Sequence DeletionGenetics0303 health sciencesReceptors NotchMESH: Androstenediols030305 genetics & heredityMESH: Infant NewbornIntracellular Signaling Peptides and ProteinsGeneral MedicineMESH: Sequence DeletionMESH: Chick EmbryoCell biologyembryonic structuresFemale[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]MESH: Membrane ProteinsSignal transductionMESH: HoloprosencephalySignal TransductionAdultmusculoskeletal diseasesCell signalingcongenital hereditary and neonatal diseases and abnormalitiesanimal structuresMolecular Sequence DataNotch signaling pathwayMESH: Sequence AlignmentBiologyArticle03 medical and health sciencesFGF8[SDV.BDD] Life Sciences [q-bio]/Development BiologyHoloprosencephalyAndrostenediolsGeneticsmedicineAnimalsHumans[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Amino Acid SequenceMolecular Biology030304 developmental biology[SDV.GEN]Life Sciences [q-bio]/GeneticsMESH: Molecular Sequence DataMESH: HumansBase SequenceInfant NewbornMembrane ProteinsMESH: Adultmedicine.diseaseMESH: MaleForebrainMutation testingMESH: Receptors NotchSequence AlignmentMESH: Femaledescription
International audience; Genetics of Holoprosencephaly (HPE), a congenital malformation of the developing human forebrain, is due to multiple genetic defects. Most genes that have been implicated in HPE belong to the sonic hedgehog signaling pathway. Here we describe a new candidate gene isolated from array comparative genomic hybridization redundant 6qter deletions, DELTA Like 1 (DLL1), which is a ligand of NOTCH. We show that DLL1 is co-expressed in the developing chick forebrain with Fgf8. By treating chick embryos with a pharmacological inhibitor, we demonstrate that DLL1 interacts with FGF signaling pathway. Moreover, a mutation analysis of DLL1 in HPE patients revealed a three-nucleotide deletion. These various findings implicate DLL1 in early patterning of the forebrain and identify NOTCH as a new signaling pathway involved in HPE.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2011-03-15 |