TlxandPax6co-operate genetically to establish the pallio-subpallial boundary in the embryonic mouse telencephalon

Abstract

We have examined the role of Tlx, an orphan nuclear receptor, in dorsal-ventral patterning of the mouse telencephalon. Tlx is expressed broadly in the ventricular zone, with the exception of the dorsomedial and ventromedial regions. The expression spans the palliosubpallial boundary, which separates the dorsal (i.e. pallium) and ventral (i.e. subpallium) telencephalon. Despite being expressed on both sides of the palliosubpallial boundary, Tlx homozygous mutants display alterations in the development of this boundary. These alterations include a dorsal shift in the expression limits of certain genes that abut at the pallio-subpallial boundary as well as the abnormal formation of the radial glial palisade that normally marks this boundary. The Tlx mutant phenotype is similar to, but less severe than, that seen in

The Orphan Nuclear Receptor TLX/NR2E1 in Neural Stem Cells and Diseases

“…Consistent with the findings in Drosophila, mouse Tlx is expressed in the developing central nervous system (CNS) from embryonic day 8 (E8) until E13.5 and in retinal progenitor cells (RPCs) from E11.5 until E17.5 during retinal development [5,[30][31][32]. At the embryonic stage, Tlx expression presents a graded pattern in the telencephalon along the dorsalventral axis with a high level in the dorsal-lateral region and a low level in the ventral-medial region [33]. Tlx is also expressed in postnatal NSCs and may activate neurogenesis in the subventricular zone of the lateral ventricle based on the findings that Tlx mutant brains have severely reduced hippocampal dentate gyri and greatly expanded lateral ventricles in adult mice [34][35][36].…”

“…Prospero, which encodes a homeodomain transcription factor associated with the differentiation of ganglion mother cells after asymmetric stem cell division of neuroblasts in the central brain [42,43], is the only target gene that has been found to be directly regulated by Tll in postembryonic stages [44]. In the mouse, multiple genes involved in the development of the CNS and visual system have been identified as Tlx targets, such as Gsh2, Pax2, Pten, p21, p57, S100b, Aqp4, Plce1, Wnt7a, microRNA-9, Bmp4, and GFAP [21,[32][33][34][35][36][37][45][46][47][48][49][50] (Table 1). Interestingly, Tlx may act as a transcriptional activator for the expression of sirt1, Wnt7a, Mash1, and Oct-3/4 based on in vitro luciferase assays and chromatin immunoprecipitation assays [16,21,[51][52][53].…”

“…In that study, TLX, LSD1, CoREST, and HDAC1/2 were suggested to form a transrepression complex at the Pten promoter to suppress Pten expression in retinal cells. Pax6 also genetically interacts with Tlx to regulate the dorsal-ventral patterning of the mouse telencephalon [33].…”

“…Tlx functions to maintain the self-renewal capacity of NSCs in mouse brain from the embryonic to the adult stage [11,33,49,59]. Studies of Tlx-knockout mice have shown that Tlx is required for neurogenesis in the superficial cortical layers and for the normal development of zinc-containing cortical circuits [60,61].…”

Identification and characterization of a novel transcript down‐regulated in Dlx1/Dlx2 and up‐regulated in Pax6 mutant telencephalon

“…In the embryonic telencephalon, the expression of Pax6 is largely confined to the mitotically active ventricular neuroepithelium of the pallium, although low expression is also present in the lateral ganglionic eminence (Stoykova et al, 1996(Stoykova et al, , 2000Toresson et al, 2000;Yun et al, 2001;Stenman et al, 2003). Cortical development is severely compromised in the Pax6 -/-mutant (Stoykova et al, 1996(Stoykova et al, , 2000Caric et al, 1997;Warren et al, 1999;Toresson et al, 2000;Yun et al, 2001).…”