title: Dlx1&2-dependent expression of Zfhx1b (Sip1, Zeb2) regulates the fate switch between cortical and striatal interneurons.
abstract: Mammalian pallial (cortical and hippocampal) and striatal interneurons are both generated in the embryonic subpallium, including the medial ganglionic eminence (MGE). Herein we demonstrate that the Zfhx1b (Sip1, Zeb2) zinc finger homeobox gene is required in the MGE, directly downstream of Dlx1&2, to generate cortical interneurons that express Cxcr7, MafB, and cMaf. In its absence, Nkx2-1 expression is not repressed, and cells that ordinarily would become cortical interneurons appear to transform toward a subtype of GABAergic striatal interneurons. These results show that Zfhx1b is required to generate cortical interneurons, and suggest a mechanism for the epilepsy observed in humans with Zfhx1b mutations (Mowat-Wilson syndrome).
authors: Department of Psychiatry, Neuroscience Program, and the Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco (UCSF), San Francisco, CA 94158-2324, USA.
authors: Gabriel L
authors: GL
authors: McKinsey
authors: Susan
authors: S
authors: Lindtner
authors: Brett
authors: B
authors: Trzcinski
authors: Axel
authors: A
authors: Visel
authors: Len A
authors: LA
authors: Pennacchio
authors: Danny
authors: D
authors: Huylebroeck
authors: Yujiro
authors: Y
authors: Higashi
authors: John L R
authors: JL
authors: Rubenstein
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000196:embryology* / Q000254:growth & development; D003342:Corpus Striatum / Q000196:embryology* / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D055495:Neurogenesis / Q000502:physiology; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C120602:ZEB2 protein, mouse; D000074165:Zinc Finger E-box Binding Homeobox 2