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Development
2000 Jul 01;12713:2945-54. doi: 10.1242/dev.127.13.2945.
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The homeodomain-containing gene Xdbx inhibits neuronal differentiation in the developing embryo.
Gershon AA
,
Rudnick J
,
Kalam L
,
Zimmerman K
.
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The development of the vertebrate nervous system depends upon striking a balance between differentiating neurons and neural progenitors in the early embryo. Our findings suggest that the homeodomain-containing gene Xdbx regulates this balance by maintaining neural progenitor populations within specific regions of the neuroectoderm. In posterior regions of the Xenopus embryo, Xdbx is expressed in a bilaterally symmetric stripe that lies at the middle of the mediolateral axis of the neural plate. This stripe of Xdbx expression overlaps the expression domain of the proneural basic/helix-loop-helix-containing gene, Xash3, and is juxtaposed to the expression domains of Xenopus Neurogenin related 1 and N-tubulin, markers of early neurogenesis in the embryo. Xdbx overexpression inhibits neuronal differentiation in the embryo and when co-injected with Xash3, Xdbx inhibits the ability of Xash3 to induce ectopic neurogenesis. One role of Xdbx during normal development may therefore be to restrict spatially neuronal differentiation within the neural plate, possibly by altering the neuronal differentiation function of Xash3.
Fig. 1. Xdbx encodes an hlx class homeodomain-containing protein. (A) The Xdbx sequence and
putative protein-coding domain are shown. The homeodomain region is underlined. The Xdbx
sequence is available through GenBank (accession number AF253504). (B) Comparison of the Xdbx
homeodomain to other members of the hlx homeodomain family. Dashes indicate conserved residues.
The genes listed include zebrafish hlx1 (Fjose et al., 1994), murine Dbx (Lu et al., 1992), chick
ChoxE (Rangini et al., 1991), murine Dbx2 (Shoji et al., 1996), murine Hlx (Allen et al., 1991) and
Drosophila H2.0 (Barad et al., 1988).
Fig. 2. Xdbx expression during Xenopus development. Whole-mount
in situ hybridization of Xdbx at stage 14 (A), stage 20 (D) and stage
28 (F). The expression domain at the midline of the axis in anterior
regions is indicated by an arrowhead (A). Cross sections of this
region are shown in C. The expression in a bilaterally symmetric
stripe in posterior regions is indicated by an arrow (A,D). Cross
sections within this region of the embryo reveal Xdbx expression at
the midpoint of the mediolateral axis of the neural plate (B) and
subsequently at the midpoint of the dorsoventral axis of the neural
tube (E). At later stages of development (stage 28, F), Xdbx
expression is prominent in anterior regions of the embryo. Cross
sections indicate that Xdbx expression is dorsally restricted within
anterior regions of this domain (G) but remains specific to the
midpoint of the dorsoventral axis within the posteriorhindbrain (H).
Note that within this region Xdbx expression is specific to cells at the
ventricular surface.
Fig. 3. Xdbx expression is restricted with regards to the mediolateral
and anteroposterior axes of the neural plate. (A) Comparison of the
anterior domain of Xdbx expression (arrowhead) to that of En-2
(asterisk) in neural plate stage embryos. (B) Comparison of Xdbx
expression (arrow and arrowhead) to that of Krox20 (asterisks) in
neurula stage embryos. (C,D) Comparison of Xdbx (arrow and
arrowhead), Xash3 (C, gray arrow) and X-Ngnr1 (D, asterisks)
expression in neural plate stage embryos. (E-G) Cross-sections of
embryo co-hybridized with Xdbx (black arrow) and Xash3 (E, gray
arrow), X-Ngnr1 (F, asterisks) and N-tubulin (G, asterisks) are shown.
Xdbx expression is marked by a red precipitate and expression of the
other genes is marked by a light-blue precipitate. Scattered light-blue
precipitate at surface in E is background BCIP reactivity resulting
from prolonged chromagenic incubation (approximately 72 hours).
(H) Effects of Xdbx overexpression on X-Ngnr1 expression. (I) Effects
of X-Ngnr1 overexpression on Xdbx expression. (H,I) Arrow indicates
injected side of the embryo. Light-blue staining represents expression
of co-injected b-gal lineage tracer.
Fig. 4. Xdbx overexpression inhibits neuronal differentiation but not
neural patterning. The effects of Xdbx overexpression on the
expression of N-tubulin (A), NeuroD (B), N-CAM (D), Xash3 (E) and
F-cadherin (F) are shown. (C) The effect of XdbxHD overexpression
on the expression of N-tubulin. In all panels, the injected side of the
embryo is indicated by an arrow. Light-blue staining represents
expression of the co-injected b-gal lineage tracer.
Fig. 5. Xdbx is not positively linked to either X-Notch1 or Xiro3. The
effects of X-Notch1/ICD (A), X-Delta1STU (B) and Xiro3 (C)
overexpression on Xdbx expression are shown. Xiro3 expression in
embryos overexpressing Xdbx (D). In all panels, the injected side of
the embryo is indicated by an arrow. Light-blue staining represents
expression of the co-injected b-gal lineage tracer.
Fig. 6. Xdbx inhibits the neuronal differentiation function of Xash3. The effects
of GR-Xash3 (A,C) injection and GR-Xash3/Xdbx (B), GRXash3/
X-Delta1STU (D) and GR-Xash3/X-Delta1STU/Xdbx
(E) co-injections on the expression of N-tubulin are shown. See Fig. 4 (A) for effects of Xdbx alone on N-tubulin expression. Arrows indicate injected side of
embryo and light blue staining represents expression of the coinjected
b-gal lineage tracer.
dbx1 (developing brain homeobox 1) gene expression in Xenopus laevis embryo, assayed via in situ hybridization, NF stage 14, dorsal view, anteriorleft.
dbx1 (developing brain homeobox 1) gene expression in Xenopus laevis embryo, assayed via in situ hybridization, NF stage 20, dorsal view, anteriorleft.
dbx1 (developing brain homeobox 1) gene expression in Xenopus laevis embryo, assayed via in situ hybridization, NF stage 28, lateral view, anteriorleft, dorsal up.