Pax6 is a transcription factor essential for the development of tissues including the eyes, central nervous system and endocrine glands of vertebrates and invertebrates. It regulates the expression of a broad range of molecules, including transcription factors, cell adhesion and short‐range cell–cell signalling molecules, hormones and structural proteins. It has been implicated in a number of key biological processes including cell proliferation, migration, adhesion and signalling both in normal development and in oncogenesis. The mechanisms by which Pax6 regulates (...) its downstream targets likely involve the use of different splice variants and interactions with multiple proteins, allowing it to generate different effects in different cells. Extrapolation to developmental transcription factors in general suggests that variation in the nature of individual factors is likely to contribute to the emergence of differences between tissues. BioEssays 24:1041–1051, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

Development requires not only the correct specification of organs and cell types in the right places (pattern), but also the control of their size and shape (growth). Many signaling pathways control both pattern and growth and how these two are distinguished has been something of a mystery. In the fly eye, a Pax6 homolog (eyeless) controls eye specification together with several other genes. Now Dominguez et al.1 show that Notch signaling controls eye growth through a second Pax6 protein (...) (Eyegone). In mice and humans the single Pax6 gene appears to encode both specification and growth controlling proteins through alternative mRNA splicing. BioEssays 26:600–603, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Pioneering molecular work on chelicerate visual system development in the horseshoe crab Limulus polyphemus surprised with the possibility that this process may not depend on the deeply conserved retinal determination function of Pax6 transcription factors. Genomic, transcriptomic, and developmental studies in spiders now reveal that the arthropod Pax6 homologs eyeless and twin of eyeless act as ancestral determinants of the ocular head segment in chelicerates, which clarifies deep gene regulatory and structural homologies and recommends more unified terminologies in (...) the comparison of arthropod visual systems. Following this phylotypic stage, chelicerate visual system development differs fundamentally from other arthropods during the compartmentalization of the ocular segment in that eye and optic neuropil primordia originate independently from each other. Comparative analyses of this phase identified further gene regulatory homologies but also major differences, most notably the possibly compensatory replacement of Pax6 by Pax2 in lateral eye specification. Also see the video abstract here: https://youtu.be/Hdfr3z5kEXU. (shrink)

In 1995, the eyeless (ey) gene was dubbed the “master‐regulator” of eye development in Drosophila. Not only is ey required for eye development, but its misexpression can convert many other tissues into eye, including legs, wings and antennae.(1) ey is remarkable for its ability to drive coordinate differentiation of the multiple cell types that have to differentiate in a very precise pattern to construct the fly eye, and for its power to override the previous differentiation programs of many other diverse (...) tissues. Even more remarkable, the ey homolog Pax6 and homologs of other eye determination genes from Drosophila are also required for eye development in vertebrates,(2,3) prompting reassessment of the evolution of vision throughout the animal kingdom.(4,5) Now Kumar and Moses have published a study that throws a new light on ey function in Drosophila.(6) According to their work, ey becomes a master regulator of eye development much later than previously thought, and is regulated by signalling through the Notch and EGFR signaling pathways. BioEssays 23:763–766, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The retina pigment epithelium (RPE) is a highly specialised epithelium that serves as a multifunctional and indispensable component of the vertebrate eye. Although a great deal of attention has been paid to its transdifferentiation capabilities and its ancillary functions in neural retina development, little is known about the molecular mechanisms that specify the RPE itself. Recent advances in our understanding of the genetic network that controls the progressive specification of the eye anlage in vertebrates have provided some of the initial (...) cues to the mechanisms responsible for RPE patterning. Here, we have outlined many recent findings that suggest that a limited number of transcription factors, including Otx2, Mitf and Pax6 and a few signalling cascades, are the elements required for the onset of RPE specification in vertebrates. Furthermore, using this information and the data available on the specification of the pigmented cells of primitive chordates, we have ventured some hypotheses on the origin of RPE cells during evolution. BioEssays 26:766–777, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

During development of the anterior eye segment, cells that originate from the surface epithelium or the neuroepithelium need to interact with mesenchymal cells, which predominantly originate from the neural crest. Failures of proper interaction result in a complex of developmental disorders such Peters' anomaly, Axenfeld–Rieger's syndrome or aniridia. Here we review the role of transcription factors that have been identified to be involved in the coordination of anterior eye development. Among these factors is PAX6, which is active in both (...) epithelial and mesenchymal cells during ocular development, albeit at different doses and times. We propose that PAX6 is a key element that synchronizes the complex interaction of cell types of different origin, which are all needed for proper morphogenesis of the anterior eye. We discuss several molecular mechanisms that might explain the effects of haploinsufficiency of PAX6 and other transcription factors, and the broad variation of the resulting phenotypes. BioEssays 26:374–386, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Pax genes are a family of development control genes that encode nuclear transcription factors. They are characterized by the presence of the paired domain, a conserved amino acid motif with DNA‐binding activity. Originally, paired‐box‐containing genes were detected in Drosophila malenogaster, where they exert multiple functions during embryogenesis. In vertebrates, Pax genes are also involved in embryogenesis. Mutations in four out of nine characterized Pax genes have been associated with either congenital human diseases such as Waardenburg syndrome (PAX3), Aniridia (PAX6), (...) Peter's anomaly (PAX6), renal coloboma syndrome (PAX2), Small eye (Pax6), (Pax21Neu), which all show defects in development. Recently, analysis of spontaneous and transgenic mouse mutants has revealed that vertebrate Pax genes are key regulators during organogenesis of kidney, eye, ear, nose, limb muscles, vertebral column and brain. Like their Drosophila counterparts, vertebrate Pax genes are involved in pattern formation during embryogenesis, possibly by determiing the time and place of organ initiation of morphogenesis. For most tissues, however, the nature of the primary development action of Pax transcription factors remains to be elucidated. One predominant theme is signal transduction during tissue interactions, which may lead to a position‐specific regulation of cell proliferation. (shrink)