Abstract
Decussation of axonal tracts is an important hallmark of vertebrate neuroanatomy resulting in one brain hemisphere controlling the contralateral side of the body and also computing the sensory information originating from that respective side. Here, we show that BMP interferes with optic chiasm formation and RGC pathfinding in zebrafish. Experimental induction of BMP4 at 15 hpf results in a complete ipsilateral projection of RGC axons and failure of commissural connections of the forebrain, in part as the result of an interaction with shh signaling, transcriptional regulation of midline guidance cues and an affected optic stalk morphogenesis. Experimental induction of BMP4 at 24 hpf, resulting in only a mild repression of forebrain shh ligand expression but in a broad expression of pax2a in the diencephalon, does not per se prevent RGC axons from crossing the midline. It nevertheless shows severe pathologies of RGC projections e.g., the fasciculation of RGC axons with the ipsilateral optic tract resulting in the innervation of one tectum by two eyes or the projection of RGC axons in the direction of the contralateral eye.
Highlights
Development of the vertebrate eye begins during late gastrulation in the prosencephalon, where an eye field is defined from which two optic vesicles evaginate [1,2,3].Consecutive optic cup morphogenesis is a dynamic process
We used a model of optic cup morphogenesis defects through induction of bmp4 expression in the zebrafish (Danio rerio) [8,31] to investigate the functional integrity of the presumptive optic nerve head
We did not identify any transcriptional changes of sonic hedgehog (Shh) ligands, receptors or Gli transcription factors in our microarray analysis, we investigated the expression of Sonic hedgehog ligand genes shha/b in response to bmp4 induction
Summary
Consecutive optic cup morphogenesis is a dynamic process. It requires an epithelial sheet migration over the distal rim of the optic cup integrating tissue from the lens-averted domain into the lens-facing domain [4,5,6,7]. Optic stalk domains are largely integrated into the optic cup via the ventral rim, which is the optic fissure [8,9]. These movements are facilitated by BMP antagonists [4,8]. The optic nerve head or optic disc, the area through which retinal ganglion cell axons exit the eye, is established at the proximal end of the optic fissure [1,2,10]
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