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Fig. 4. Atr2 is required for patterning the ventral forebrain and for expression of
patterning signals by the anterior notochord and the ANR during E8. (A) A
normal E9.5 embryo expresses Nkx2.1 in the ventral forebrain. (B) An
om mutant littermate shows reduced Nkx2.1 expression. (C) At
E8.5, Pax6 is excluded from the anterior neural plate (red
arrowheads). (D) In om mutants, Pax6 is abnormally expanded
across the anterior midline (red arrowhead). (E) At E8.5, Emx2 is
excluded from the anterior midline (arrowheads). (F) om mutants
express Emx2 across the anterior neural midline (arrowhead). (G) At
E8.75, Shh is diminished in the anterior region of om
mutants (left) compared with in normal littermates (right), except for a small
spot (arrowhead). (H) At E8.0, Shh is expressed in the full extent of
the developing midline, nearly reaching the anteriormost edge of the neural
plate (red arrow). (I) In E8.0 mutants, Shh expression is reduced
anteriorly. The anterior edge of the neural plate is indicated (red arrow).
(J) Gli1 is reduced in the anterior region of the om mutant
(left) compared with wild type (right). (K) Gli3 is normally absent
from the midline of the neural plate at E8.75 (arrowheads), as seen in this
transverse slice through the hindbrain. (L) In om, Gli3 is expanded
toward the midline (arrowheads). (M) At E9.5, transverse sections show
Shh in the spinal cord floorplate and the notochord (nc) of a
wild-type embryo. The floorplate is thinner than the lateral wall (compare red
lines). (N) In om mutants at E9.5, Shh is expressed normally
but the notochord is enlarged and the floorplate has not thinned (red lines).
(O,P) At E9.5, Hnf3b is expressed in the ventral spinal cord in both
normal (O) and mutant (P) embryos; mutants have enlarged notochords and an
absence of floorplate. Ventral neurocoels are outlined in yellow. (Q)
Hnf3b expression in a wild-type embryo at E8.5. (R) Hnf3b is
expressed normally in om embryos. (S) Brachyury marks the developing
notochord at E8.25. (T) om mutants express brachyury normally at
E8.25. (U) At E8.5, goosecoid is expressed in the anterior midline. (V)
om mutants express goosecoid in a wild-type pattern. (W-Y)
Parasagittal sections of the anterior neural plate of E8.5 embryos stained
with Fgf8. Dorsal is up, anterior is right. Epidermal ectoderm is
outlined in green, neural tissue in yellow. (W) In wild type, Fgf8
transcripts are tightly localized to the anterior neural ridge (ANR; red
circle). (X,Y) In om embryos, Fgf8 expression is decreased
in the ANR (red circles), and is shifted into the adjacent epidermal ectoderm
and neurectoderm. (Z) At E8.5, Hesx1 is expressed in the anterior
neural plate up to the ANR (yellow line). (Z') In om embryos,
Hesx1 expression is reduced laterally and is absent from the
anteriormost neural plate (yellow arrowheads).
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