Emx2andPax6Function in Cooperation withOtx2andOtx1to Develop Caudal Forebrain Primordium That Includes Future Archipallium

Abstract

One of the central issues in developmental neurobiology is how the forebrain is organized ontogenetically. The traditional view is that the anterior neuroectoderm first develops into mesencephalic and prosencephalic vesicles; the latter vesicle subsequently develops into the diencephalon and secondary prosencephalon, of which dorsal parts protrude to generate the telencephalon. The diencephalon yields the pretectum, thalamus, and prethalamus, and the telencephalon produces the archipallium, neopallium, and ganglionic eminences. By identifying cell descendants that once expressed Emx2 with use of the Cre knock-in mutant into the Emx2 locus and analyzing phenotypes of double mutants between Emx2 and Otx2/Otx1 and between Emx2 and Pax6, we propose that at the 3-6 somite stage, the anterior neuroectoderm develops into three primordia: midbrain, caudal forebrain, and rostral forebrain. The caudal forebrain primordium generates not only the pretectum, thalamus, and prethalamus but also the archipallium, cortical hem, choroid plexus, choroidal roof, and eminentia thalami. The primordium corresponds to the Emx2-or Pax6-positive region at the 3-6 somite stage that most probably does not include the future neopallium or commissural plate. Otx2 and Otx1 that are expressed in the entire future forebrain and midbrain cooperate with this Emx2 and Pax6 expression in the development of the caudal forebrain primordium; Emx2 and Pax6 functions are redundant. In the embryonic day 9.5 Emx2 Ϫ/Ϫ Pax6 Ϫ/Ϫ double mutant, the caudal forebrain remained unspecified and subsequently transformed into tectum in a mirror image of the endogenous one.

Essential roles of the histone methyltransferase ESET in the epigenetic control of neural progenitor cells during development

“…ESET flox (f) (Matsui et al, 2010), Emx2-Cre (Kimura et al, 2005) and Nes-Cre (Isaka et al, 1999) mice were described previously. Emx2-Cre;ESET(f/+) or Nes-Cre;ESET(f/+) male mice were crossed with ESET(f/f) female mice, and the day when a vaginal plug was observed was scored as embryonic day (E) 0.5.…”

Differentially expressed genes are marked by histone 3 lysine 9 trimethylation in human cancer cells

“…The medulloblastoma cell line D283 represents the classic histopathological subtype of these tumors that contain an amplified OTX2 homeobox gene (Boon et al, 2003(Boon et al, , 2005Acampora et al, 2005;de Haas et al, 2006). OTX2 is an essential transcriptional factor in the development of the central nervous system (Kimura et al, 2005;Vernay et al, 2005;Rath et al, 2006). Results from D283 were also contrasted with Daoy, a cell line isolated from the nodular/desmoplastic subtype of medulloblastoma.…”

The same enhancer regulates the earliestEmx2expression in caudal forebrain primordium, subsequent expression in dorsal telencephalon and later expression in the cortical ventricular zone

“…CDB0018K) mutants and Cre knock-in mutant mice at the Emx2 locus (Accession No. CDB0020K) were established previously and genotyped as described (http://www.cdb.riken.jp/arg/mutant%20mice%20list.html) (Matsuo et al, 1995;Yoshida et al, 1997;Kimura et al, 2005). ROSA26R mice were obtained from Jackson Laboratory (http://jaxmice.jax.org/strain/ 003474.html).…”

“…At E12.5, the cells in prethalamus, thalamus and noncommissure region of the pretectum are descendants of the cells that once expressed Emx2 (Kimura et al, 2005). However, after E9.5, Emx2 expression does not occur in the majority of the diencephalon.…”

“…Emx2;Otx2 and Emx2;Pax6 double mutants displayed Emx2 functions in diencephalon development (Suda et al, 2001;Kimura et al, 2005). Emx1;Emx2 double mutants indicated Emx functions in the development of medial pallium (Pellegrini et al, 1996;Yoshida et al, 1997;Shinozaki et al, 2004); they also showed their roles in cortical lamination (Shinozaki et al, 2002).…”