The transcription factor Nfix is essential for normal brain development

Campbell, Christine E., Piper, Michael, Plachez, Celine, Yeh, Yu-Ting, Baizer, Joan S., Osinski, Jason M., Litwack, E David, Richards, Linda J. and Gronostajski, Richard M. (2008) The transcription factor Nfix is essential for normal brain development. BMC Developmental Biology, 8 52: 1-18. doi:10.1186/1471-213X-8-52

Author Campbell, Christine E.
Piper, Michael
Plachez, Celine
Yeh, Yu-Ting
Baizer, Joan S.
Osinski, Jason M.
Litwack, E David
Richards, Linda J.
Gronostajski, Richard M.
Title The transcription factor Nfix is essential for normal brain development
Formatted title
The transcription factor Nfix is essential for normal brain development
Journal name BMC Developmental Biology   Check publisher's open access policy
ISSN 1471-213X
Publication date 2008-05-13
Year available 2008
Sub-type Article (original research)
DOI 10.1186/1471-213X-8-52
Open Access Status DOI
Volume 8
Issue 52
Start page 1
End page 18
Total pages 18
Editor Norton, Melissa
Place of publication London
Publisher BioMed Central Ltd.
Language eng
Subject C1
920111 Nervous System and Disorders
110902 Cellular Nervous System
110903 Central Nervous System
Abstract Background: The Nuclear Factor I (NFI) multi-gene family encodes site-specific transcription factors essential for the development of a number of organ systems. We showed previously that Nfia-deficient mice exhibit agenesis of the corpus callosum and other forebrain defects; Nfib-deficient mice have defects in lung maturation and show callosal agenesis and forebrain defects resembling those seen in Nfia-deficient animals, while Nficdeficient mice have defects in tooth root formation. Recently the Nfix gene has been disrupted and these studies indicated that there were largely uncharacterized defects in brain and skeletal development in Nfix-deficient mice. Results: Here we show that disruption of Nfix by Cre-recombinase mediated excision of the 2nd exon results in defects in brain development that differ from those seen in Nfia and Nfib KO mice. In particular, complete callosal agenesis is not seen in Nfix-/- mice but rather there appears to be an overabundance of aberrant Pax6- and doublecortin-positive cells in the lateral ventricles of Nfix-/- mice, increased brain weight, expansion of the cingulate cortex and entire brain along the dorsal ventral axis, and aberrant formation of the hippocampus. On standard lab chow Nfix-/- animals show a decreased growth rate from ~P8 to P14, lose weight from ~P14 to P22 and die at ~P22. If their food is supplemented with a soft dough chow from P10, Nfix-/- animals show a lag in weight gain from P8 to P20 but then increase their growth rate. A fraction of the animals survive to adulthood and are fertile. The weight loss correlates with delayed eye and ear canal opening and suggests a delay in the development of several epithelial structures in Nfix-/- animals. Conclusion: These data show that Nfix is essential for normal brain development and may be required for neural stem cell homeostasis. The delays seen in eye and ear opening and the brain morphology defects appear independent of the nutritional deprivation, as rescue of perinatal lethality with soft dough does not eliminate these defects.
Keyword Developmental Biology
Developmental Biology
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 102645
Institutional Status UQ

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Created: Wed, 30 Jul 2008, 02:16:47 EST