The homeodomain transcription factor Nkx2. gene expression patterns that then generate defined neuronal and glial populations. Dorsal progenitors express homeobox genes of the empty spiracles (whereas the ventral progenitors are known to express homeobox genes of the and in developing embryonic lungs40. In the embryonic brain, Nkx2.1 controls the specification of the GABAergic interneurons and oligodendrocytes that populate the ventral and dorsal telencephalic region3,16,37,41,42,43. Loss of BS-181 HCl Nkx2.1 leads to ventral-to-dorsal re-specification of the pallium causing loss of GABAergic interneurons and oligodendrocytes in the dorsal telencephalic region16,17,37. Recently, we Rabbit polyclonal to GAPDH.Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing arole in glycolysis and nuclear functions, respectively. Participates in nuclear events includingtranscription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due tothe nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such asSIRT1, HDAC2 and PRKDC (By similarity). Glyceraldehyde-3-phosphate dehydrogenase is a keyenzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate showed that Nkx2.1 regulates the generation of astrocytes that populate the ventral telencephalon during embryonic development and participates in axonal guidance in the anterior commissure18,44. We found that this Nkx2.1-derived astrocyte population is generated from three ventral telencephalic precursor regions, namely the medial ganglionic eminence (MGE), the anterior entopeduncular area (AEP)/preoptic area (POA) and the triangular septal nucleus (TS)18,44. Several works have revealed information on the origin of embryonic NG2 glia, also known as polydendrocytes or oligodendrocyte precursor cells45,46. Our work contributed by showing that embryonic NG2 glia originate from the Nkx2.1+ progenitors of the ventral telencephalon and promote precise blood vessel network development44. These cells have a highly complex branched morphology and are different from neurons, mature oligodendrocytes, astrocytes and microglia45,46,47,48,49,50,51,52. For a clear distinction, these cells will BS-181 HCl be referred to as NG2 glia in this study. Here, we describe that Nkx2.1-derived astrocytes populate the corpus callosum (CC) and its surrounding regions in the embryonic dorsal telencephalon. These Nkx2.1-derived astrocytes are generated from E12.5 onwards with maximal production between E14.5 to E16.5. Interestingly, in BrdU incorporation showed that interestingly Nkx2.1 regulates astroglial generation by controlling the proliferation of Nkx2.1+ precursors. Similarly, neurosphere differentiation assays showed decreased generation of astroglia from Nkx2.1?/? precursors, which may be a result of decreased proliferation of astroglial precursors upon loss of Nkx2. 1 or perhaps defects in glial specification and/or differentiation. In addition, chromatin immunoprecipitation analysis showed that Nkx2.1 binds to the promoter of the glial fibrillary acidic protein (promoter construct confirmed that Nkx2.1 binds to the GFAP promoter and regulates expression of the gene. Thus, Nkx2.1 exhibits multilevel control over the generation of the dorsal telencephalic astroglia by spatially coordinating astroglial generation from three ventral precursor regions BS-181 HCl and temporally restricting maximal generation to E14.5 to E16.5. Further analysis into the complete BS-181 HCl repertoire of genes regulated by Nkx2.1 will shed light on the exact mode of action and help to delineate the different mechanisms involved in astrogliogenesis. Results Nkx2.1-derived astrocytes populate the dorsal telencephalon during development Nkx2.1-positive (Nkx2.1+) progenitors of the MGE, AEP/POA and septal nucleus generate embryonic GABAergic interneurons and oligodendrocytes BS-181 HCl that populate the ventral and dorsal telencephalon3,16,37,41,42,43. Our recent results have shown that Nkx2.1 additionally regulates the production of astrocytes and NG2 glia that populate the ventral telencephalon18,44. Further immunostaining of the subpallial transcription factor Nkx2.1 revealed strong expression in several differentiated cells within and around the CC in the dorsal telencephalon from E16.5 to E18.5 (n?=?8; Fig. 1aCg). To differentiate the Nkx2.1+ cell types in the CC region we made use of several cell-type-specific transgenic strains. Figure 1 The.