Cux2 functions downstream of Notch signaling to regulate dorsal interneuron formation in the spinal cord.
Obtaining the diversity of interneuron subtypes in their appropriate numbers requires the orchestrated integration of progenitor proliferation with the regulation of differentiation. Here we demonstrate through loss-of-function studies in mice that the Cut homeodomain transcription factor Cux2 (Cutl2) plays an important role in regulating the formation of dorsal spinal cord interneurons. Furthermore, we show that Notch regulates Cux2 expression. Although Notch signaling can be inhibitory to the expression of proneural genes, it is also required for interneuron formation during spinal cord development. Our findings suggest that Cux2 might mediate some of the effects of Notch signaling on interneuron formation. Together with the requirement for Cux2 in cell cycle progression, our work highlights the mechanistic complexity in balancing neural progenitor maintenance and differentiation during spinal cord neurogenesis.
Iulianella
Angelo
A
Stowers Institute for Medical Research, 1000 E. 50th Street, Kansas City, MO 64110, USA. ani@stowers.org
Sharma
Madhulika
M
Vanden Heuvel
Greg B
GB
Trainor
Paul A
PA
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D017931:DNA Primers / Q000235:genetics; D046149:Embryo Culture Techniques; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D018398:Homeodomain Proteins; D051881:Receptor, Notch1; C499317:Ascl1 protein, mouse; C101672:Cux2 protein, mouse; C497762:Notch1 protein, mouse