Runx1 selectively regulates cell fate specification and axonal projections of dorsal root ganglion neurons.
Runx1-deficient mice die around embryonic day 11.5 due to impaired hematopoiesis. This early death prevents the analysis of the role of Runx1 in the development of sensory ganglia. To overcome the early embryonic lethality, we adopted a new approach to utilize transgenic Runx1-deficient mice in which hematopoietic cells are selectively rescued by Runx1 expression under the control of GATA-1 promoter. In Runx1-deficient mice, the total number of dorsal root ganglion (DRG) neurons was increased, probably because of an increased proliferative activity of DRG progenitor cells and decreased apoptosis. In the mutant DRG, TrkA-positive neurons and peptidergic neurons were increased, while c-ret-positive neurons were decreased. Axonal projections were also altered, in that both central and peripheral projections of CGRP-positive axons were increased. In the dorsal horn of the spinal cord, projections of CGRP-positive axons expanded to the deeper layer, IIi, from the normal terminal area, I/IIo. Our results suggest that Runx1 is involved in the cell fate specification of cutaneous neurons, as well as their projections to central and peripheral targets.
Yoshikawa
Masaaki
M
Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
Senzaki
Kouji
K
Yokomizo
Tomomasa
T
Takahashi
Satoru
S
Ozaki
Shigeru
S
Shiga
Takashi
T
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D050676:Core Binding Factor Alpha 2 Subunit / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050982:GATA1 Transcription Factor / Q000235:genetics; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D012867:Skin / Q000196:embryology / Q000294:innervation / Q000378:metabolism
D050676:Core Binding Factor Alpha 2 Subunit; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; C493726:Runx1 protein, mouse; D020917:Receptor, trkA; D015740:Calcitonin Gene-Related Peptide