Trends in Genetics
Volume 16, Issue 6, 1 June 2000, Pages 237-240
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Positioning the isthmic organizer: where Otx2 and Gbx2 meet

https://doi.org/10.1016/S0168-9525(00)02000-XGet rights and content

Abstract

Regional diversity along the anterior–posterior axis of the central nervous system is established during gastrulation and is subsequently refined by local organizing centres that are located at genetically defined positions. The isthmic organizer possesses midbrain- and cerebellum-inducing properties, and its positioning at the midbrain–hindbrain boundary is a crucial event that controls midbrain and cerebellum development. Recent work has shown that two transcription factors, Otx2 and Gbx2, are instrumental in positioning the isthmic organizer at the midbrain–hindbrain boundary.

Section snippets

The positioning of the isthmic organizer is controlled by Otx2 and Gbx2

An organizer is thought to be established gradually within a tissue by a series of steps that first specify different fields and then produce morphogenetic properties at their boundaries8, 9. These properties include the expression of specific genes, the production of morphogenetic molecules and the ability to generate cell diversity. Once a boundary has been defined between two different fields, co-operative cell–cell interactions might eventually produce signalling molecules that activate

A genetic cascade

The proper establishment of the isthmic organizer is defined not just by these two transcription factors but rather by a complex cascade of genetic interactions (Fig. 1). The presumptive fore–midbrain and the prospective rostral hindbrain are visualized at 7.75 days post coitum (d.p.c) by the expression of Otx2 and Gbx2, respectively (Fig. 1). After this, En1, Wnt1 and Fgf8 are activated in broad areas along the posterior midbrain and the rostral hindbrain, and then their expression becomes

Acknowledgements

I wish to thank D. Acampora and M. Brand for interesting discussion on this topic. I am also grateful to A. Secondulfo for typing the manuscript.

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      At the primitive streak stage in mouse and chick embryos (Niss and Leutz, 1998; Wassarman et al., 1997), gbx2 is expressed in the posterior neural plate and negatively interacts with otx2, which is expressed in the anterior neural plate. Mutual repression between these two genes contributes to the positioning of the midbrain-hindbrain boundary (MHB) (Simeone, 2000), which works as the local organizer patterning the midbrain and cerebellum (Nakamura et al., 2005; Rhinn and Brand, 2001) and thus called the isthmic organizer. Importantly, mouse embryos lacking Gbx2 in rhombomere 1 (r1) after embryonic stage 9 (E9) still developed the cerebellum, although the expression of the isthmic organizer genes remained dependent on Gbx2, suggesting a distinct requirement for this gene in cerebellum formation (Li et al., 2002).

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