TY - JOUR
T1 - Transcriptional regulation of Nfix by NFIB drives astrocytic maturation within the developing spinal cord
AU - Matuzelski, Elise
AU - Bunt, Jens
AU - Harkins, Danyon
AU - Lim, Jonathan W.C.
AU - Gronostajski, Richard M.
AU - Richards, Linda J.
AU - Harris, Lachlan
AU - Piper, Michael
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/12/15
Y1 - 2017/12/15
N2 - During mouse spinal cord development, ventricular zone progenitor cells transition from producing neurons to producing glia at approximately embryonic day 11.5, a process known as the gliogenic switch. The transcription factors Nuclear Factor I (NFI) A and B initiate this developmental transition, but the contribution of a third NFI member, NFIX, remains unknown. Here, we reveal that ventricular zone progenitor cells within the spinal cord express NFIX after the onset of NFIA and NFIB expression, and after the gliogenic switch has occurred. Mice lacking NFIX exhibit normal neurogenesis within the spinal cord, and, while early astrocytic differentiation proceeds normally, aspects of terminal astrocytic differentiation are impaired. Finally, we report that, in the absence of Nfia or Nfib, there is a marked reduction in the spinal cord expression of NFIX, and that NFIB can transcriptionally activate Nfix expression in vitro. These data demonstrate that NFIX is part of the downstream transcriptional program through which NFIA and NFIB coordinate gliogenesis within the spinal cord. This hierarchical organisation of NFI protein expression and function during spinal cord gliogenesis reveals a previously unrecognised auto-regulatory mechanism within this gene family.
AB - During mouse spinal cord development, ventricular zone progenitor cells transition from producing neurons to producing glia at approximately embryonic day 11.5, a process known as the gliogenic switch. The transcription factors Nuclear Factor I (NFI) A and B initiate this developmental transition, but the contribution of a third NFI member, NFIX, remains unknown. Here, we reveal that ventricular zone progenitor cells within the spinal cord express NFIX after the onset of NFIA and NFIB expression, and after the gliogenic switch has occurred. Mice lacking NFIX exhibit normal neurogenesis within the spinal cord, and, while early astrocytic differentiation proceeds normally, aspects of terminal astrocytic differentiation are impaired. Finally, we report that, in the absence of Nfia or Nfib, there is a marked reduction in the spinal cord expression of NFIX, and that NFIB can transcriptionally activate Nfix expression in vitro. These data demonstrate that NFIX is part of the downstream transcriptional program through which NFIA and NFIB coordinate gliogenesis within the spinal cord. This hierarchical organisation of NFI protein expression and function during spinal cord gliogenesis reveals a previously unrecognised auto-regulatory mechanism within this gene family.
KW - Astrocyte
KW - GFAP
KW - Gliogenesis
KW - NFIA
KW - NFIB
KW - NFIX
KW - Nuclear Factor I
KW - Spinal cord
UR - http://www.scopus.com/inward/record.url?scp=85032995580&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2017.10.019
DO - 10.1016/j.ydbio.2017.10.019
M3 - Article
C2 - 29106906
AN - SCOPUS:85032995580
SN - 0012-1606
VL - 432
SP - 286
EP - 297
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -