Crossinhibitory activities of Ngn1 and Math1 allow specification of distinct dorsal interneurons.
Distinct classes of neurons are generated from progenitor cells distributed in characteristic dorsoventral patterns in the developing spinal neural tube. We define restricted neural progenitor populations by the discrete, nonoverlapping expression of Ngn1, Math1, and Mash1. Crossinhibition between these bHLH factors is demonstrated and provides a mechanism for the generation of discrete bHLH expression domains. This precise control of bHLH factor expression is essential for proper neural development since as demonstrated in both loss- and gain-of-function experiments, expression of Math1 or Ngn1 in dorsal progenitor cells determines whether LH2A/B- or dorsal Lim1/2-expressing interneurons will develop. Together, the data suggest that although Math1 and Ngn1 appear to be redundant with respect to neurogenesis, they have distinct functions in specifying neuronal subtype in the dorsal neural tube.
Gowan
K
K
Center for Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Helms
A W
AW
Hunsaker
T L
TL
Collisson
T
T
Ebert
P J
PJ
Odom
R
R
Johnson
J E
JE
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D015723:Gene Library; D018257:Helix-Loop-Helix Motifs; D007395:Interneurons / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology*; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C500943:Atoh1 protein, mouse; C486336:Neurog1 protein, mouse