TY - JOUR
T1 - N-twist, an evolutionarily conserved bHLH protein expressed in the developing CNS, functions as a transcriptional inhibitor
AU - Verzi, Michael P.
AU - Anderson, Joshua P.
AU - Dodou, Evdokia
AU - Kelly, Kathleen K.
AU - Greene, Stephanie B.
AU - North, Brian J.
AU - Cripps, Richard M.
AU - Black, Brian L.
N1 - Funding Information:
We thank John Rubenstein (UCSF) for the Mash1 and neuroge-nin2 probes, for helpful discussions, and for providing a critical review of the manuscript. We are grateful to Tom Kornberg and Brian Biehs (UCSF) for providing the Drosophila engrailed and wingless probes. M.V. and K.K. were supported by predoctoral fellowships from the Howard Hughes Medical Institute and the American Heart Association-Desert Mountain Affiliate, respectively. E.D. was supported by a postdoctoral fellowship from the American Heart Association-Western States Affiliate. This work was supported by grants from the NIH to R.M.C. and B.L.B.
PY - 2002
Y1 - 2002
N2 - Members of the basic helix-loop-helix (bHLH) transcription factor family play an essential role in multiple developmental processes. During neurogenesis, positive and negative regulation by bHLH proteins is essential for proper development. Here we report the identification and initial characterization of the bHLH gene, Neuronal twist (N-twist), named for its neural expression pattern and high sequence homology and physical linkage to the mesodermal inhibitor, M-twist. N-twist is expressed in the developing mouse central nervous system in the midbrain, hindbrain, and neural tube. This neural expression is conserved in invertebrates, as expression of the Drosophila ortholog of N-twist is also restricted to the central nervous system. Like other bHLH family members, N-Twist heterodimerizes with E protein and binds DNA at a consensus bHLH-binding site, the E box. We show that N-Twist inhibits MASH1-dependent transcriptional activation by sequestering E protein in a dominant negative fashion. Thus, these studies support the notion that N-Twist represents a novel negative regulator of neurogenesis.
AB - Members of the basic helix-loop-helix (bHLH) transcription factor family play an essential role in multiple developmental processes. During neurogenesis, positive and negative regulation by bHLH proteins is essential for proper development. Here we report the identification and initial characterization of the bHLH gene, Neuronal twist (N-twist), named for its neural expression pattern and high sequence homology and physical linkage to the mesodermal inhibitor, M-twist. N-twist is expressed in the developing mouse central nervous system in the midbrain, hindbrain, and neural tube. This neural expression is conserved in invertebrates, as expression of the Drosophila ortholog of N-twist is also restricted to the central nervous system. Like other bHLH family members, N-Twist heterodimerizes with E protein and binds DNA at a consensus bHLH-binding site, the E box. We show that N-Twist inhibits MASH1-dependent transcriptional activation by sequestering E protein in a dominant negative fashion. Thus, these studies support the notion that N-Twist represents a novel negative regulator of neurogenesis.
UR - http://www.scopus.com/inward/record.url?scp=0036385790&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036385790&partnerID=8YFLogxK
U2 - 10.1006/dbio.2002.0753
DO - 10.1006/dbio.2002.0753
M3 - Article
C2 - 12217327
AN - SCOPUS:0036385790
VL - 249
SP - 174
EP - 190
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 1
ER -