Elsevier

Progress in Neurobiology

Volume 65, Issue 5, December 2001, Pages 473-488
Progress in Neurobiology

Regionalisation and acquisition of polarity in the optic tectum

https://doi.org/10.1016/S0301-0082(01)00015-6Get rights and content

Abstract

The optic tectum differentiates from the alar plate of the mesencephalon and receives retinal fibres in a precise retinotopic manner. Here, mechanisms of tectum polarisation and regionalisation are reviewed. Misexpression of Pax2, Pax5 or En can change the fate of the presumptive diencephalon to that of the tectum. Ephrin A2 and A5 are expressed in a gradient in the tectum, caudal high and rostral low, and may play important roles in the formation of a precise retinotectal projection map. Retinal fibres that express receptors for these ligands, and which come from the temporal retina, are repulsed by the ligands and do not invade the caudal tectum. Both En1 and En2 can regulate posterior characteristics in the tectum by inducing ephrin A2 and A5. Transplantation experiments in chick have indicated that the mes/metencephalic boundary works as an organiser for the tectum and the cerebellum. Fgf8 is a candidate signalling molecule in the organiser. Pax2/5, En, and Fgf8 are in a positive feedback loop for their expression such that misexpression of one of these genes in the diencephalon turns on the feedback loop and can result in induction of an optic tectum. Otx2 and Gbx2 appear to repress each other's expression and contribute to defining the posterior border of the tectum. Misexpression of Otx2 in the metencephalon can change the fate of its alar plate to a tectum, and misexpression of Gbx2 in the mesencephalon can cause anterior shifting of the caudal limit of the tectum. The anterior border of the tectum may be determined as a result of repressive interactions between Pax6 and En1/Pax2. Along the dorsoventral axis of the mesencephalon, Shh contributes to ventralize the tissue; that is, Shh can change the fate of the presumptive tectum to that of the tegmentum that is the ventral structure. It is proposed that the brain vesicle that expresses Otx2, Pax2, and En1 may differentiate into the tectum.

Introduction

Following neural induction, neural tissue forms a simple neural tube, from which the complicated structure of the vertebrate central nervous system (CNS) arises. Brain vesicle formation is the first obvious sign of regionalisation. First, three brain vesicles form: prosencephalon, mesencephalon and rhombencephalon. Then the vesicles gradually subdivide. The prosencephalon subdivides into the telencephalon and the diencephalon, and the rhombencephalon subdivides into the metencephalon and the myelencephalon. It is generally accepted that: (1) the combination of the transcription factors may determine the fate of the region; and (2) vertical and planner signals act to change or fix the expression of the transcription factors. I will consider the nature of the signals and how the tissue responds to these signals in determining the combination of the transcription factors, and I will review regionalisation and the polarity formation of the optic tectum.

Section snippets

Organiser for the tectum

An organiser for the mesencephalon and the metencephalon has been identified and defined using classical transplantation between quail and chick embryos. Alvarado-Mallart and Sotelo (1984) transplanted the mesencephalic alar plate to the diencephalon at stage 10 of Hamburger and Hamilton's (1951) staging series, and showed that the transplant kept its original fate and differentiated into the tectum. The optic tectum is the visual centre in lower vertebrates, and Alvarado-Mallart and Sotelo

Genes expressed in the tectum

In Fig. 1, expression of some representative genes in the mesencephalic region around stage 10 is shown. En1 and En2, which are the homologue of Drosophila segment polarity gene engrailed, are expressed in the metencephalon and the mesencephalon (Davis and Joyner, 1988, Gardner et al., 1988, Patel et al., 1989). En2 is expressed in a gradient of rostral high and caudal low in the mesencephalon. In En1 knock-out mice, the tectum and the cerebellum are reduced (Wurst et al., 1994). En1 expression

Molecules responsible for pathfinding of the retinal fibres

The optic tectum is the visual centre of lower vertebrates, and receives retinal fibres in a precise retinotopic manner. Fibres from the nasal part of the retina project to the caudal part of the tectum, and those from the temporal retina project to the rostral tectum (Fig. 2, Crossland and Uchwat, 1979). Since Sperry (1963) proposed a chemoaffinity theory, researchers tried to search for the molecule responsible for the target recognition of the retinal fibres. Bonhoeffer's group devised an

Definement of the mes/metencephalic boundary

Otx2 and Gbx2 are expressed from the very early stage of vertebrate development (Simeone et al., 1992, Bally-Cuif et al., 1995a, Bally-Cuif et al., 1995b, Bouillet et al., 1995, Shamim and Mason, 1998, Niss and Leutz, 1998). Otx2 is expressed at the prosencephalon and the mesencephalon and is suggested to play an important role in the determination of these regions. At the gastrulation stage, Otx2 is expressed rostral to the Hensen's node (Simeone et al., 1992, Bally-Cuif et al., 1995b), and

Dorso-ventral patterning

Shh is expressed in the notochord and induces a floor plate in the neural tube. Then its expression is induced in the floor plate cells in the entire CNS. It was suggested that Shh acts as a morphogen to induce ventral cell types in the spinal cord, that is, cells that receive a high Shh signal differentiate into the floorplate, cells that receive a medium signal differentiate into motor neurons; and ones that receive a low Shh signal differentiate into some ventral interneurons (reviewed in

General discussion

From the results of misexpression experiments, it is assumed that the neural tube in the brain region that expresses En, Pax2 and Otx2 may differentiate into the midbrain (Fig. 5A). This assumption explains the experimental results carried out so far. Misexpression experiments showed that Fgf8, En, and Pax2/5 are in the positive feedback loop for their expression (Fig. 5B) (Crossley et al., 1996, Martinez et al., 1999, Shamim et al., 1999, Funahashi et al., 1999, Okafuji et al., 1999, Araki and

Conclusion

The fate of the brain vesicles may be determined by the combination of the transcription factors. The region where Otx2, En1, and Pax2 are expressed differentiates into the tectum. Mhb works as an organiser for the tectum and the cerebellum. The candidate signalling molecule is Fgf8, which may stabilise or change the combination of the transcription factors and organise the tectum in the mesencephalon and the cerebellum in the metencephalon. The nature of the organising signal and the

Acknowledgements

I thank all my colleagues for their co-operation.

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