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Figure 3 | Neural Development

Figure 3

From: A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct emx2 mutant phenotype

Figure 3

Mutants found in the thalamocortical screen display a variety of defects in the TCA projection. (A) Intercross breeding scheme for recessive thalamocortical mutant screen. ENU, N-ethyl-N-nitrosourea; wt, wild type. (B) A control E18.5 brain stained with X-Gal shows a neatly organized array of TCAs grown from the dorsal thalamus (dTh) through the ventral telencephalon (vTel) into cortex (ctx). The hippocampus (hip) fills the lateral ventricle. (C) A fuddle mutant brain shows hollow lateral ventricles (v) due to hippocampal hypoplasia, and a partial TCA defect in which a very thin TCA fascicle is misrouted ventrally in vTel (red arrow). (D) A magoo mutant has a small forebrain with a thick bundle of TCAs misrouted into vTel (red arrow). (E) The wanderer mutant displays a small cortex and a large bundle of TCAs misrouted ventrally near the DTB (red arrow). (F) A sprawl brain shows disorganized and overfasciculated TCAs in the lateral vTel, some of which appear stalled (red arrow). (G) In a baffled mutant brain TCAs are disorganized in lateral vTel (long red arrow), and appear stalled near the corticostriatal boundary (CSB; short red arrow). (H, H') In a bumpy mutant brain, TCAs project normally to the cortex, but some aberrantly invade the cortical plate to innervate ectopia on the surface of the cortex (red arrows). (I) A thin sagittal section through an E18.5 bumpy mutant cortical ectopia stained for hematoxylin and eosin (H&E) shows cells erupted through the marginal zone (mz) and pia. iz, intermediate zone; sp, subplate. (I') A different section through the same ectopia was stained for axon fibers with neurofilament-M (NFM). Normal fibers can be seen approaching the cortex (black arrowheads), and within the deep cortical layers (black arrow), but fibers are also present in the ectopia (red arrow). Scale bar, 250 μm. (B-H) show one hemisphere of the caudal half of E18.5 G3 brains, cut coronally at the internal capsule. 'ot' indicates optic tract in (E, H), normal in all mutants.

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