title: Progressive Differentiation and Instructive Capacities of Amniotic Fluid and Cerebrospinal Fluid Proteomes following Neural Tube Closure.
abstract: After neural tube closure, amniotic fluid (AF) captured inside the neural tube forms the nascent cerebrospinal fluid (CSF). Neuroepithelial stem cells contact CSF-filled ventricles, proliferate, and differentiate to form the mammalian brain, while neurogenic placodes, which generate cranial sensory neurons, remain in contact with the AF. Using in vivo ultrasound imaging, we quantified the expansion of the embryonic ventricular-CSF space from its inception. We developed tools to obtain pure AF and nascent CSF, before and after neural tube closure, and to define how the AF and CSF proteomes diverge during mouse development. Using embryonic neural explants, we demonstrate that age-matched fluids promote Sox2-positive neurogenic identity in developing forebrain and olfactory epithelia. Nascent CSF also stimulates SOX2-positive self-renewal of forebrain progenitor cells, some of which is attributable to LIFR signaling. Our Resource should facilitate the investigation of fluid-tissue interactions during this highly vulnerable stage of early brain development.
authors.affiliation: Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA; Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Chau
authors.affiliation: Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Springel
authors.affiliation: Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Broadbelt
authors.affiliation: Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hye-Yeon
authors.initials: HY
authors.lastname: Park
authors.affiliation: Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Salih
authors.initials: S
authors.lastname: Topal
authors.affiliation: Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Melody P
authors.initials: MP
authors.lastname: Lun
authors.affiliation: Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Hillary
authors.initials: H
authors.lastname: Mullan
authors.affiliation: Department of Pharmacology and Physiology, Institute for Neuroscience, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Maynard
authors.affiliation: Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Hanno
authors.initials: H
authors.lastname: Steen
authors.affiliation: Department of Pharmacology and Physiology, Institute for Neuroscience, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: LaMantia
authors.affiliation: Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA; Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA. Electronic address: maria.lehtinen@childrens.harvard.edu.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Lehtinen
mesh_terms: D000653:Amniotic Fluid / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D005260:Female; D051379:Mice; D054259:Neural Tube / Q000378:metabolism*; D046569:Neuroepithelial Cells / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D011247:Pregnancy; D020543:Proteome / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology
chemical_list: D020543:Proteome