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. 2012 Mar 6;6:7. doi: 10.3389/fnana.2012.00007

Figure 1.

Figure 1

Disorders of AP patterning in the brain stem.(A) Anteroposterior patterning and the Isthmus Organizer. Regionalization of the brain starts with the formation of patterning centers that secrete signaling molecules such as the fibroblast growth factors (FGFs). Fgf8 and Fgr17 are important signaling molecules at both the anterior forebrain and the MB-HB junction. In the forebrain, it helps to direct formation of the prefrontal cortex and other rostral structures by inducing cells to secrete the transcription factor Pax6. At the MB-HB junction, the patterning center known as the isthmus organizer (IsO) is localized and induced to secrete Fgf8 and Fgf17 by the interaction of transcription factor Gbx2 from the rhombencephalon and Otx2 from the caudal mesencephalon. The secretion of Fgf8 and Fgf17 then induces further changes crucial to formation of the MB-HB junction and the formation of the cerebellum. The junction of the diencephalon (di) and mesencephalon (mes) is directed by the interaction of Pax6 from the diencephalon and En1/Pax2 from the rostral mesencephalon. Repression of Otx2 expression by FGF8 induces Gbx2 formation to establish the location of the MB-HB junction and can affect cerebellar formation, as the cerebellum forms from the most rostral portion of the HB. Similarly, alterations of Pax6 or En1/Pax2 will alter the location of the diencephalic-mesencephalic junction. (Adapted from Barkovich and Raybaud, 2012). (B) Sagittal T1 weighted image shows a short MB, long pons, and large superior vermis (black arrows), suggesting an abnormality of anteroposterior patterning with rostral misplacement of the Isthmus Organizer. In addition, the patient has agenesis of the corpus callosum. (C) Sagittal T1 weighted image shows a slightly small pons and a short, thick medulla (white arrows) with an abnormal pontomedullary transition. This is postulated to result from mixed gains and losses of rhombomere expression in the developing rhombencephalon or potentially a segmental shift of rhombomeres. (D) Sagittal T2 weighted image shows a very elongated MB (white arrows) with small, short pons (black arrow), and small cerebellar vermis, suggesting caudal displacement of the Isthmus Organizer due to abnormal anterioposterior patterning from overexpression of Otx2.