BMP Signaling Interferes with Optic Chiasm Formation and Retinal Ganglion Cell Pathfinding in Zebrafish

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.

Zebrafish as a Model for Neurological Disorders

“…Moreover, using heptanol, a well-known gap junction blocker, the authors showed that calcium wave propagation, but not initiation, required fully functional gap junctions. Knickmeyer et al [10] investigated the role of bone morphogenetic protein (BMP) signaling, especially BMP4, in optic nerve pathfinding using a transgenic line encoding the zebrafish bmp4 gene under the heat-inducible hsp70 promoter, allowing precise overexpression timing. The authors thereby showed that BMP signaling was dynamic and overexpression of bmp4 impaired both the elongation of optic nerves and their crossing at the optic chiasm, suggesting for the first time a requirement for BMP signaling in retinal ganglion cell projections to the brain.…”