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Dmrt5, a Novel Neurogenic Factor, Reciprocally Regulates Lhx2 to Control the Neuron-Glia Cell-Fate Switch in the Developing Hippocampus

Muralidharan, B; Keruzore, M; Pradhan, SJ; Roy, B; Shetty, AS; Kinare, V; D'Souza, L; ... Tole, S; + view all (2017) Dmrt5, a Novel Neurogenic Factor, Reciprocally Regulates Lhx2 to Control the Neuron-Glia Cell-Fate Switch in the Developing Hippocampus. Journal of Neuroscience , 37 (46) pp. 11245-11254. 10.1523/JNEUROSCI.1535-17.2017. Green open access

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Abstract

Regulation of the neuron–glia cell-fate switch is a critical step in the development of the CNS. Previously, we demonstrated that Lhx2 is a necessary and sufficient regulator of this process in the mouse hippocampal primordium, such that Lhx2 overexpression promotes neurogenesis and suppresses gliogenesis, whereas loss of Lhx2 has the opposite effect. We tested a series of transcription factors for their ability to mimic Lhx2 overexpression and suppress baseline gliogenesis, and also to compensate for loss of Lhx2 and suppress the resulting enhanced level of gliogenesis in the hippocampus. Here, we demonstrate a novel function of Dmrt5/Dmrta2 as a neurogenic factor in the developing hippocampus. We show that Dmrt5, as well as known neurogenic factors Neurog2 and Pax6, can each not only mimic Lhx2 overexpression, but also can compensate for loss of Lhx2 to different extents. We further uncover a reciprocal regulatory relationship between Dmrt5 and Lhx2, such that each can compensate for loss of the other. Dmrt5 and Lhx2 also have opposing regulatory control on Pax6 and Neurog2, indicating a complex bidirectionally regulated network that controls the neuron–glia cell-fate switch.

Type: Article
Title: Dmrt5, a Novel Neurogenic Factor, Reciprocally Regulates Lhx2 to Control the Neuron-Glia Cell-Fate Switch in the Developing Hippocampus
Open access status: An open access version is available from UCL Discovery
DOI: 10.1523/JNEUROSCI.1535-17.2017
Publisher version: http://doi.org/10.1523/JNEUROSCI.1535-17.2017
Language: English
Additional information: Copyright © 2017 Muralidharan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Keywords: Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, cell fate, glia, hippocampus, neuron, TRANSCRIPTION FACTOR, PRECURSOR CELLS, CEREBRAL-CORTEX, EXPRESSION, GENES, ASTROGLIOGENESIS, PROGENITOR, PAX6, GLIOGENESIS, ASTROCYTES
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10040418
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