Isthmic Organizer

The Isthmic Organizer, also known as the midbrain/hindbrain boundary (MHB), is a secondary organizer region that develops at the junction of the Mesencephalon and Metencephalon. The MHB expresses signaling molecules that regulate the differentiation and patterning of the adjacent neuroepithelium. This allows for the development of the midbrain and hindbrain as well as the specification of neuronal subtypes in these regions. The fact that the MHB is sufficient for the development of the mid and hindbrain was shown in an experiment where quail MHB cells transplanted into the forebrain of a chick were able to induce an ectopic midbrain and cerebellum.

The development and location of the MHB is mediated by the transcription factors Otx2 and Gbx2.Otx2 is expressed in the anterior neural tube and cells in the posterior neural tube express Gbx2. These two homeodomain transcription factors are activated by Irx1 and then cross inhibit one another in the developing central nervous system(CNS). This leads to the creation of a defined boundary that becomes the isthmic organizer region after the neural tube closes.