Mxi1 is essential for neurogenesis in Xenopus and acts by bridging the pan-neural and proneural genes.
We have isolated and characterized Xenopus Mxi1, a member of the Myc/Max/Mad family of bHLHZip transcription factors. Xmxi1 transcripts are present during gastrulation and early neurula stages, earlier and in broader domains as compared to the neuronal determination factor neurogenin (X-ngnr-1). Consistent with an early role in neurogenesis, Xmxi1 is positively regulated by Sox3, SoxD, and proneural genes, as well as negatively by the Notch pathway. Loss-of-function experiments demonstrate an essential role for Xmxi1 in the establishment of a mature neural state that can be activated by factors that induce neuronal differentiation, such as SoxD and X-ngnr-1. Overexpression of Xmxi1 in Xenopus embryos results in ectopic activation of Sox3, an early pan-neural marker of proliferating neural precursor cells. Within the neural plate, the neuronal differentiation marker N-tubulin and cell cycle control genes such as XPak3 and p27(Xic1) are inhibited, but the expression of early determination and differentiation markers, including X-ngnr-1 and X-MyT1, is not affected. Inhibition of neuronal differentiation by Xmxi1 is only transient, and, at early tailbud stages, both endogenous and ectopic neurogenesis are observed. While Xmxi1 enhances cell proliferation and apoptosis in the early Xenopus embryo, both activities appear not to be required for the function of Xmxi1 in primary neurogenesis.
Klisch
Tiemo J
TJ
DFG-Center of Molecular Physiology of the Brain, Department of Developmental Biochemistry, University of Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen, Germany.
Souopgui
Jacob
J
Juergens
Kathrin
K
Rust
Barbara
B
Pieler
Tomas
T
Henningfeld
Kristine A
KA
D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002490:Central Nervous System / Q000196:embryology*; D018076:DNA, Complementary; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D017403:In Situ Hybridization; D008954:Models, Biological; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D038081:Organogenesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014981:Xenopus / Q000196:embryology* / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins; D018076:DNA, Complementary; D025521:Tumor Suppressor Proteins; C079440:MXI1 protein, human