Ascl1 defines sequentially generated lineage-restricted neuronal and oligodendrocyte precursor cells in the spinal cord.
The neural basic helix-loop-helix transcription factor Ascl1 (previously Mash1) is present in ventricular zone cells in restricted domains throughout the developing nervous system. This study uses genetic fate mapping to define the stage and neural lineages in the developing spinal cord that are derived from Ascl1-expressing cells. We find that Ascl1 is present in progenitors to both neurons and oligodendrocytes, but not astrocytes. Temporal control of the fate-mapping paradigm reveals rapid cell-cycle exit and differentiation of Ascl1-expressing cells. At embryonic day 11, Ascl1 identifies neuronal-restricted precursor cells that become dorsal horn neurons in the superficial laminae. By contrast, at embryonic day 16, Ascl1 identifies oligodendrocyte-restricted precursor cells that distribute throughout the spinal cord. These data demonstrate that sequentially generated Ascl1-expressing progenitors give rise first to dorsal horn interneurons and subsequently to late-born oligodendrocytes. Furthermore, Ascl1-null cells in the spinal cord have a diminished capacity to undergo neuronal differentiation, with a subset of these cells retaining characteristics of immature glial cells.
Battiste
James
J
Center for Basic Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Helms
Amy W
AW
Kim
Euiseok J
EJ
Savage
Trisha K
TK
Lagace
Diane C
DC
Mandyam
Chitra D
CD
Eisch
Amelia J
AJ
Miyoshi
Goichi
G
Johnson
Jane E
JE
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D002454:Cell Differentiation; D017931:DNA Primers / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D019426:Integrases / Q000096:biosynthesis / Q000235:genetics; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism*; D011247:Pregnancy; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D019426:Integrases; D013629:Tamoxifen; C499317:Ascl1 protein, mouse; C045073:Cre recombinase