Foxd1 is required for proper formation of the optic chiasm
Author:
Herrera Eloísa1, Marcus Riva1, Li Suzanne2, Williams Scott E.1, Erskine Lynda3, Lai Eseng2, Mason Carol1
Affiliation:
1. Departments of Pathology, Anatomy and Cell Biology and Center for Neurobiology and Behavior, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA 2. Cell Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA 3. Departments of Visual Science and Molecular Genetics, Institute of Ophthalmology, University College London, London EC1V 9EL, UK
Abstract
In animals with binocular vision, retinal ganglion cell (RGC) axons from each eye sort in the developing ventral diencephalon to project to ipsi- or contralateral targets, thereby forming the optic chiasm. Ipsilaterally projecting axons arise from the ventrotemporal (VT) retina and contralaterally projecting axons primarily from the other retinal quadrants. The winged helix transcription factor Foxd1 (previously known as BF-2, Brain Factor 2) is expressed in VT retina, as well as in the ventral diencephalon during the formation of the optic chiasm. We report here that in embryos lacking Foxd1,both retinal development and chiasm morphogenesis are disrupted. In the Foxd1 deficient retina, proteins designating the ipsilateral projection, such as Zic2 and EphB1, are missing, and the domain of Foxg1 (BF-1) expands from nasal retina into the VT crescent. In retina-chiasm co-cultures, VT RGCs from Foxd1 deficient retina are not repulsed by chiasm cells, and in vivo many VT RGCs aberrantly project contralaterally. However, even though the ipsilateral program is lost in the retina, a larger than normal uncrossed component develops in Foxd1 deficient embryos. Chiasm defects include axon stalling in the chiasm and a reduction in the total number of RGCs projecting to the optic tract. In addition, in the Foxd1 deficient ventral diencephalon, Foxg1 invades the Foxd1 domain, Zic2 and Islet1 expression are minimized, and Slit2 prematurely expands, changes that could contribute to axon projection errors. Thus, Foxd1 plays a dual role in the establishment of the binocular visual pathways: first, in specification of the VT retina, acting upstream of proteins directing the ipsilateral pathway; and second, in the patterning of the developing ventral diencephalon where the optic chiasm forms.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference36 articles.
1. Brown, A., Yates, P. A., Burrola, P., Ortuno, D., Vaidya, A.,Jessell, T. M., Pfaff, S. L., O'Leary, D. D. and Lemke, G.(2000). Topographic mapping from the retina to the midbrain is controlled by relative but not absolute levels of EphA receptor signaling. Cell102,77-88. 2. Brown, L. Y., Kottman, A. H. and Brown, S.(2003). Immunolocalization of Zic2 expression in the developing forebrain. Gene Expr. Patterns3, 361-367. 3. Chung, K. Y., Shum, D. K. and Chan, S. O.(2000). Expression of chondroitin sulfate proteoglycans in the chiasm of mouse embryos. J. Comp. Neurol.417,153-163. 4. Clark, K. L., Halay, E. D., Lai, E. and Burley, S. K.(1993). Co-crystal of the HNF-3/forkhead DNA-recognition motif resembles histone H5. Nature364,412-420. 5. Erskine, L., Williams, S. E., Brose, K., Kidd, T., Rachel, R. A., Goodman, C. S., Tessier-Lavigne, M. and Mason, C. A.(2000). Retinal ganglion cell axon guidance in the mouse optic chiasm: expression and function of robos and slits. J. Neurosci.20,4975-4982.
Cited by
102 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|