The basic helix-loop-helix transcription factor TCF4 impacts brain architecture as well as neuronal morphology and differentiation
Standard
The basic helix-loop-helix transcription factor TCF4 impacts brain architecture as well as neuronal morphology and differentiation. / Schoof, Melanie; Hellwig, Malte; Harrison, Luke; Holdhof, Dörthe; Lauffer, Marlen C; Niesen, Judith; Virdi, Sanamjeet; Indenbirken, Daniela; Schüller, Ulrich.
in: EUR J NEUROSCI, Jahrgang 51, Nr. 11, 06.2020, S. 2219-2235.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - The basic helix-loop-helix transcription factor TCF4 impacts brain architecture as well as neuronal morphology and differentiation
AU - Schoof, Melanie
AU - Hellwig, Malte
AU - Harrison, Luke
AU - Holdhof, Dörthe
AU - Lauffer, Marlen C
AU - Niesen, Judith
AU - Virdi, Sanamjeet
AU - Indenbirken, Daniela
AU - Schüller, Ulrich
N1 - © 2020 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
PY - 2020/6
Y1 - 2020/6
N2 - Germline mutations in the basic helix-loop-helix transcription factor 4 (TCF4) cause the Pitt-Hopkins syndrome (PTHS), a developmental disorder with severe intellectual disability. Here, we report findings from a new mouse model with a central nervous system-specific truncation of Tcf4 leading to severe phenotypic abnormalities. Furthermore, it allows the study of a complete TCF4 knockout in adult mice, circumventing early postnatal lethality of previously published mouse models. Our data suggest that a TCF4 truncation results in an impaired hippocampal architecture affecting both the dentate gyrus as well as the cornu ammonis. In the cerebral cortex, loss of TCF4 generates a severe differentiation delay of neural precursors. Furthermore, neuronal morphology was critically affected with shortened apical dendrites and significantly increased branching of dendrites. Our data provide novel information about the role of Tcf4 in brain development and may help to understand the mechanisms leading to intellectual deficits observed in patients suffering from PTHS.
AB - Germline mutations in the basic helix-loop-helix transcription factor 4 (TCF4) cause the Pitt-Hopkins syndrome (PTHS), a developmental disorder with severe intellectual disability. Here, we report findings from a new mouse model with a central nervous system-specific truncation of Tcf4 leading to severe phenotypic abnormalities. Furthermore, it allows the study of a complete TCF4 knockout in adult mice, circumventing early postnatal lethality of previously published mouse models. Our data suggest that a TCF4 truncation results in an impaired hippocampal architecture affecting both the dentate gyrus as well as the cornu ammonis. In the cerebral cortex, loss of TCF4 generates a severe differentiation delay of neural precursors. Furthermore, neuronal morphology was critically affected with shortened apical dendrites and significantly increased branching of dendrites. Our data provide novel information about the role of Tcf4 in brain development and may help to understand the mechanisms leading to intellectual deficits observed in patients suffering from PTHS.
KW - Animals
KW - Facies
KW - Hippocampus
KW - Humans
KW - Hyperventilation
KW - Intellectual Disability/genetics
KW - Mice
KW - Neurons
KW - Transcription Factor 4/genetics
U2 - 10.1111/ejn.14674
DO - 10.1111/ejn.14674
M3 - SCORING: Journal article
C2 - 31919899
VL - 51
SP - 2219
EP - 2235
JO - EUR J NEUROSCI
JF - EUR J NEUROSCI
SN - 0953-816X
IS - 11
ER -