Transcription factor Lhx2 is necessary and sufficient to suppress astrogliogenesis and promote neurogenesis in the developing hippocampus

Subramanian, Lakshmi, Sarkar, Anindita, Shetty, Ashwin S., Muralidharan, Bhavana, Padmanabhan, Hari, Piper, Michael, Monuki, Edwin S., Bach, Ingolf, Gronostajski, Richard M., Richards, Linda J. and Tole, Shubha (2011) Transcription factor Lhx2 is necessary and sufficient to suppress astrogliogenesis and promote neurogenesis in the developing hippocampus. Proceedings of the National Academy of Sciences of the United States of America, 108 27: E-265-E-274. doi:10.1073/pnas.1101109108


Author Subramanian, Lakshmi
Sarkar, Anindita
Shetty, Ashwin S.
Muralidharan, Bhavana
Padmanabhan, Hari
Piper, Michael
Monuki, Edwin S.
Bach, Ingolf
Gronostajski, Richard M.
Richards, Linda J.
Tole, Shubha
Title Transcription factor Lhx2 is necessary and sufficient to suppress astrogliogenesis and promote neurogenesis in the developing hippocampus
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2011-07-05
Sub-type Article (original research)
DOI 10.1073/pnas.1101109108
Open Access Status Not Open Access
Volume 108
Issue 27
Start page E-265
End page E-274
Total pages 10
Editor Clifford J. Tabin
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Collection year 2012
Language eng
Abstract The sequential production of neurons and astrocytes from neuroepithelial precursors is a fundamental feature of central nervous system development. We report that LIM-homeodomain (LIM-HD) transcription factor Lhx2 regulates this transition in the developing hippocampus. Disrupting Lhx2 function in the embryonic hippocampus by in utero electroporation and in organotypic slice culture caused the premature production of astrocytes at stages when neurons are normally generated. Lhx2 function is therefore necessary to suppress astrogliogenesis during the neurogenic period. Furthermore, Lhx2 overexpression was sufficient to suppress astrogliogenesis and prolong the neurogenic period. We provide evidence that Lhx2 overexpression can counteract the instructive astrogliogenic effect of Notch activation. Lhx2 overexpression was also able to override and suppress the activation of the GFAP promoter by Nfia, a Notch-regulated transcription factor that is required for gliogenesis. Thus, Lhx2 appears to act as a “brake” on Notch/Nfia-mediated astrogliogenesis. This critical role for Lhx2 is spatially restricted to the hippocampus, because loss of Lhx2 function in the neocortex did not result in premature astrogliogenesis at the expense of neurogenesis. Our results therefore place Lhx2 as a central regulator of the neuron-glia cell fate decision in the hippocampus and reveal a striking regional specificity of this fundamental function within the dorsal telencephalon.
Keyword Neural precursor cells
Cerebral-cortex
Gene-expression
Neuronal differentiation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2012 Collection
School of Biomedical Sciences Publications
 
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Created: Fri, 26 Aug 2011, 09:49:23 EST by Dr Michael Piper on behalf of Queensland Brain Institute