Retinal axon misrouting at the optic chiasm in mice with neural tube closure defects

In a new mouse mutant, circletail (Crc), failure of neural tube closure (em bryonic day [E] 8-9) is associated with errors in retinal axon projection a t the optic chiasm (E12-18), such that many axons normally projecting contr alaterally instead grow to ipsilateral targets, Although the architecture o f the chiasmatic region is altered, neurons and glia containing putative cu es for axon guidance are present. The aberrant ipsilateral-projecting cells originate from a nonrandom expansion of the wild-type uncrossed retinal re gion. These axon pathway defects are found in two other mutants with cephal ic neural tube defects (NTD), loop-tail (Lp) and Pax3 (splotch; Sp(2H)). Cr c is phenotypically similar to Lp, exhibiting an open neural tube from midb rain to tail (craniorachischisis), while splotch has spina bifida with or w ithout a cranial NTD, The retinal axon abnormalities occur only in the pres ence of NTD and not in homozygous mutants lacking cranial NTD, Thus, failur e of neural tube closure is associated with failure of many retinal axons t o cross the ventral midline, This study therefore reveals an unexpected con nection between closure of the neural tube at the dorsal midline and develo pment of Ventral axon tracts, genesis 27:32-47, 2000, (C) 2000 Wiley-Liss, Inc.