Foxd1 is required for proper formation of the optic chiasm Journal Article
| Authors: | Herrera, E.; Marcus, R.; Li, S.; Williams, S. E.; Erskine, L.; Lai, E.; Mason, C. |
| Article Title: | Foxd1 is required for proper formation of the optic chiasm |
| 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. |
| Keywords: | controlled study; protein expression; unclassified drug; dna-binding proteins; nonhuman; protein domain; forkhead transcription factors; mouse; phenotype; animals; mice; mice, knockout; animal tissue; cells, cultured; embryo; animal experiment; animal model; nerve tissue proteins; transcription factor; embryo development; embryo pattern formation; morphogenesis; in vivo study; cell differentiation; animalia; gene expression regulation, developmental; retina; cell count; foxg1; developmental disorder; homeodomain protein; zinc finger protein; transcription factor foxg1; visual disorder; optic chiasm; axons; retina ganglion cell; retinal ganglion cells; eye development; nerve projection; coculture; bf-1; tissue culture; ephrin b1; transcription factor foxd1; retina development; brain factor 1; priority journal; article; bf-2; brain factor 2; ephb1; foxd1; retinal axon divergence; zic2; slit protein; transcription factor islet2; transcription factor zic2; binocular vision; optic tract |
| Journal Title: | Development |
| Volume: | 131 |
| Issue: | 22 |
| ISSN: | 0950-1991 |
| Publisher: | Company of Biologists |
| Date Published: | 2004-11-01 |
| Start Page: | 5727 |
| End Page: | 5739 |
| Language: | English |
| DOI: | 10.1242/dev.01431 |
| PROVIDER: | scopus |
| PUBMED: | 15509772 |
| DOI/URL: | |
| Notes: | Development (Cambridge) -- Cited By (since 1996):54 -- Export Date: 16 June 2014 -- CODEN: DEVPE -- Source: Scopus |
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