Fig. 3. Adult PlexA1 mutant mice
outperform controls in dexterous
manipulation tasks. (A) Mouse
performing the capellini handling test.
Guiding and grasping hands are indicated by green and red arrows,
respectively. (B to D) Results of the
capellini handling test in 2-month-old
control (PlexA1fl/+;AAV1-Cre, n = 10)
and PlexA1fl/fl; AAV1-Cre (n = 10)
mice during 4 testing days. Rate of
adjustment is the average number of
paw adjustments per piece/eating
time. **P < 0.01, ***P < 0.001. (E to
G) A mouse during the grasping test.
Food pellets are indicated by black
arrows. (H and I) Grasping success and
consumption time in 3-month-old control
(PlexA1fl/+;AAV1-Cre, n = 3; and PlexA1fl/fl;
AAV1-td, n = 4) and PlexA1fl/fl;AAV1-Cre
(n = 8) mice over 4 testing days. **P <
0.01. (J and K) Quantification and
frequency distributions of pellet consumption time by control (145 trials) and
PlexA1fl/fl;AAV1-Cre (251 trials) mice.
Fig. 4. Expression of PLEXA1 in layer 5 of the motor cortex in mice
and humans, and FEZF2-mediated repression. (A) ZFPM2 (FOG2) (layer 6
marker) (15) and PLEXA1 in the human motor cortex at 20 pcw assessed
by means of in situ hybridization. (B) Sequence conservation of putative
PlexA1 cis-regulatory elements. Multispecies DNA sequence alignment
showing examples of FEZF2 CTNCANCN binding sites (top, blue bar and box)
and CGCCGC binding sites (bottom, red bar and box). The motifs are
highlighted by gray-filled boxes. (C) Luciferase activity of reporter constructs
in a 293Tcell line (expressing endogenous human Fezf2) with or without
cotransfection with a human FEZF2-expressing vector. Error bars represent
the SEM of triplicate experiments. *P < 0.05. (D to G) Analysis of
transgenic mice using a 5-kb region upstream from the first exon of the
human PLEXA1 gene or mutated human FEZF2 binding sequences. (E and
G) High magnification view of the boxed areas in (D) and (F), respectively.
(H to L) Summary of the axonal trajectories and CS connectivity within the
cervical spinal cord in wild-type and PlexA1fl/fl;Emx1-Cre mice, and in humans.
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