TY - JOUR
T1 - NFIX regulates neural progenitor cell differentiation during hippocampal morphogenesis
AU - Heng, Yee Hsieh Evelyn
AU - McLeay, Robert C.
AU - Harvey, Tracey J.
AU - Smith, Aaron G.
AU - Barry, Guy
AU - Cato, Kathleen
AU - Plachez, Céline
AU - Little, Erica
AU - Mason, Sharon
AU - Dixon, Chantelle
AU - Gronostajski, Richard M.
AU - Bailey, Timothy L.
AU - Richards, Linda J.
AU - Piper, Michael
N1 - Funding Information:
This work was supported by National Health and Medical Research Council (NHMRC) project grants (grant number 1003462 to M.P., grant number 569504 to L.J.R.) and by National Institute of Health and NYSTEM grants (grant numbers HL080624 and C026429 to R.M.G.). The following authors were supported by NHMRC fellowships: M.P. (Biomedical Career Development Fellowship); L.J.R. (Principal Research Fellowship). Y.H.E.H. was supported by a University of Queensland International scholarship.
PY - 2014/1
Y1 - 2014/1
N2 - Neural progenitor cells have the ability to give rise to neurons and glia in the embryonic, postnatal and adult brain. During development, the program regulating whether these cells divide and self-renew or exit the cell cycle and differentiate is tightly controlled, and imbalances to the normal trajectory of this process can lead to severe functional consequences. However, our understanding of the molecular regulation of these fundamental events remains limited. Moreover, processes underpinning development of the postnatal neurogenic niches within the cortex remain poorly defined. Here, we demonstrate that Nuclear factor one X (NFIX) is expressed by neural progenitor cells within the embryonic hippocampus, and that progenitor cell differentiation is delayed within Nfix-/- mice. Moreover, we reveal that the morphology of the dentate gyrus in postnatal Nfix-/- mice is abnormal, with fewer subgranular zone neural progenitor cells being generated in the absence of this transcription factor. Mechanistically, we demonstrate that the progenitor cell maintenance factor Sry-related HMG box 9 (SOX9) is upregulated in the hippocampus of Nfix-/- mice and demonstrate that NFIX can repress Sox9 promoter-driven transcription. Collectively, our findings demonstrate that NFIX plays a central role in hippocampal morphogenesis, regulating the formation of neuronal and glial populations within this structure.
AB - Neural progenitor cells have the ability to give rise to neurons and glia in the embryonic, postnatal and adult brain. During development, the program regulating whether these cells divide and self-renew or exit the cell cycle and differentiate is tightly controlled, and imbalances to the normal trajectory of this process can lead to severe functional consequences. However, our understanding of the molecular regulation of these fundamental events remains limited. Moreover, processes underpinning development of the postnatal neurogenic niches within the cortex remain poorly defined. Here, we demonstrate that Nuclear factor one X (NFIX) is expressed by neural progenitor cells within the embryonic hippocampus, and that progenitor cell differentiation is delayed within Nfix-/- mice. Moreover, we reveal that the morphology of the dentate gyrus in postnatal Nfix-/- mice is abnormal, with fewer subgranular zone neural progenitor cells being generated in the absence of this transcription factor. Mechanistically, we demonstrate that the progenitor cell maintenance factor Sry-related HMG box 9 (SOX9) is upregulated in the hippocampus of Nfix-/- mice and demonstrate that NFIX can repress Sox9 promoter-driven transcription. Collectively, our findings demonstrate that NFIX plays a central role in hippocampal morphogenesis, regulating the formation of neuronal and glial populations within this structure.
KW - Glia
KW - Glial fibrillary acidic protein
KW - Neural progenitor cell
KW - Nuclear factor one X
KW - SOX9
UR - http://www.scopus.com/inward/record.url?scp=84885176164&partnerID=8YFLogxK
U2 - 10.1093/cercor/bhs307
DO - 10.1093/cercor/bhs307
M3 - Article
C2 - 23042739
AN - SCOPUS:84885176164
SN - 1047-3211
VL - 24
SP - 261
EP - 279
JO - Cerebral Cortex
JF - Cerebral Cortex
IS - 1
ER -