Gastrulation Brain Homeobox 2 (GBX2) is a homeobox gene involved in the normal development of rhombomeres 1-3 which is the mid/hindbrain region. This gene is a dosage dependent transcription factor involved in the regulation of proper expression of other genes. GBX2 expression occurs during gastrulation and continues to be expressed in the later stages of embryogenesis. During these different stages, GBX2 is responsible for several important processes. In the neural plate stage GBX2 is required in order for the anterior hindbrain precursors to survive and form correctly. Also at this stage in development GBX2 is required for the proper regulation of different gene expression needed for the early establishment of A/P patterning in the neural plate. In the early stages of brain morphogenesis GBX2 is required for both the normal development of the anterior hindbrain and the proper formation of the mid/hindbrain organizer. Because of the effects on the mid/hindbrain organizer, GBX2 is involved in the positioning of the expression domain for isthmicFGF8. Since this is a dosage dependent gene, the different amounts of gene present in certain location can cause different outcomes. FGF8 is affected by the different dosages in the location it is expressed. The absence of GBX2 causes FGF8 expression is shifted caudally and over expression of GBX2 causes FGF8 expression to be shifted rostrally. Not all of the rhombomeres GBX2 is expressed in require the same strictness of dose regulation. Of the three, rhombomere 2 has the most strict dose requirements. Researchers have conducted knockout model research on this gene. From these experiments they have found that the loss of function of GBX2 causes the failure of many structures to form, such as the isthmic nuclei, the cerebellum, motor nerve V and many other derivatives of rhombomeres 1-3. The research has also shown that the embryos will continue to develop and will reach full term pregnancy. The babies are born but if there is a lack of GBX2 expression all will die soon after birth.
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