Figure 2.

Neural tube defects found in Zic2^kd/kd mice. (a) Lateral views of P0 Zic2^+/+ (Left) and Zic2^kd/kd (Right) newborns. Heads of Zic2^kd/kd animals were significantly smaller (microcephaly). Arrowhead, pes equinus; *, spina bifida. (b) Dorsal close-up view of the P0 Zic2^kd/kd embryo. Spina bifida was always observed. (c) Lateral close-up view. Tails were irregularly curled. (d–g) Transverse sections through thoracic (d and e) and lumbar spinal cord (f and g) of Zic2^+/+ (d and f) and Zic2^kd/kd (e and g) E15.5 embryos. drg, Dorsal root ganglion; sc, spinal cord; osc, open spinal cord; v, vertebral body. (h and i) Scanning electron micrographs show no closure of lumbar spinal cord in Zic2^kd/kd embryos (i) at E9.5 and successful closure in an E9.5 Zic2^+/+ counterpart (h). np, Posterior neuropore. (j–s) Holoprosencephaly found in the Zic2^kd/kd embryo. Coronal (j and k) and parasagittal (l and m) sections through cerebrum of Zic2^+/+ (j and l) and Zic2^kd/kd (k and m) E15.5 brain. Cerebral cortex (cc) of both hemispheres in Zic2^kd/kd brain is fused at the dorsal midline, with the single ventricle and the juxtaposed ganglionic eminence (ge) (k). Cerebral cortex and olfactory bulb (ob) of Zic2^kd/kd brain are hypoplastic (m). Magnified frontal views of head (n and o) and horizontal sections through eye (p–s) of Zic2^+/+ (n, p, and r) and Zic2^kd/kd (o, q, and s) E10.5 embryo. The telencephalic roof plate region in p and q is magnified in r and s, respectively. Telencephalic roof plate (arrowheads in n, p, and r) is apparently absent in Zic2^kd/kd animals (arrowheads in o and q), resulting in the loss of discrimination between left and right telencephalic vesicles. (t and u) A typical example of exencephaly found in the E12.5 Zic2^kd/kd embryo. p, Lateral view; q, dorsal view. Telencephalic (t), diencephalic (d), and mesencephalic (m) neural plate fail to fuse at the midline [indicated by Ex (exencephaly)]. The spinal cord remains open in the lumbosacral region (*). (v) Lateral view of Zic2^kd/kd embryo (E18.5) possessing anencephaly (arrowheads) and spina bifida (*). (w) Top view of embryo in v. In this particular animal, almost all brain tissue was lost.