Vax genes ventralize the embryonic eye

Abstract

The vertebrate retina and optic nerve are strikingly different in terms of their size, organization, and cellular diversity, yet these two structures develop from the same embryonic neuroepithelium. Precursor cells in the most ventral domain of this epithelium give rise only to the astrocytes of the optic nerve, whereas immediately adjacent, more dorsal precursors give rise to the myriad cell types of the retina. We provide genetic evidence that two closely related, ventrally expressed homeodomain proteins-Vax1 and Vax2-control this neuroepithelial segregation. In the absence of both proteins, we find that the optic nerve is transformed in its entirety into fully differentiated retina. We demonstrate that this transformation results from the loss of ventralizing actvity in the developing eye field, and that ventralization is mediated, at least in part, via Vax repression of the Pax6 gene, a potent inducer of retinal development.

Acoel development supports a simple planula-like urbilaterian

“…One interesting candidate is the homeobox gene vax (ventral anterior homeobox). This gene was named after the location and function in chordate embryos, where it is responsible for the ventralization of the retina in mouse and Xenopus (Barbieri et al 1999;Mui et al 2005). In acoels, ClVax is expressed in the ventral anterior ectoderm of the hatchling between the anterior tip and the mouth opening in a pattern remarkable similar to that seen in vertebrates ( figure 4h,i ).…”

Compartmentalization of Vertebrate Optic Neuroephithelium: External Cues and Transcription Factors

“…+/-mice, Pax6 is elevated in the vOS, which is transformed into NR (Mui et al, 2005). Ectopically expressed Pax6 was also shown to inhibit the development of the vOS in chick OV, consequently posi-tioning the eyes in a more ventral direction (Leconte et al, 2004).…”

“…However, the Vax binding site is distinct from the Pax6 auto-regulatory element, which is also a target of Pax2 (Schwarz et al, 2000). Although Pax6 is abnormally elevated in ectopic NR in the OS territory of Vax1/2-double-knockout (dko) mice, Pax2 expression is still detectable in the OV and ectopic NR of Vax1/2-dko embryos (Mui et al, 2005), suggesting that Vax and Pax2 might function independently in the optic neuroepithelium in the acquisition of OS fate.…”

“…Vax1 and Vax2 repress the expression of Pax6 by directly binding to a NR-specific intronic enhancer of Pax6 (Mui et al, 2005). However, the Vax binding site is distinct from the Pax6 auto-regulatory element, which is also a target of Pax2 (Schwarz et al, 2000).…”

“…Therefore, transforming the OS entirely into NR requires disruption of both Vax1 and Vax2 in mice and zebrafish (Mui et al, 2005;Take-uchi et al, 2003). Vax1 and Vax2 repress the expression of Pax6 by directly binding to a NR-specific intronic enhancer of Pax6 (Mui et al, 2005).…”