Characterization of progenitor domains in the developing mouse thalamus

Abstract

To understand the molecular basis of the specification of thalamic nuclei, we analyzed the expression patterns of various transcription factors and defined progenitor cell populations in the embryonic mouse thalamus. We show that the basic helix-loop-helix (bHLH) transcription factor Olig3 is expressed in the entire thalamic ventricular zone and the zona limitans intrathalamica (ZLI). Next, we define two distinct progenitor domains within the thalamus, which we name pTH-R and pTH-C, located caudal to the ZLI. pTH-R is immediately caudal to the ZLI and expresses Nkx2.2, Mash1, and Olig3. pTH-C is caudal to pTH-R and expresses Ngn1, Ngn2, and Olig3. Short-term lineage analysis of Olig3-, Mash1-, Ngn1-, and Ngn2-expressing progenitor cells as well as tracing the Pitx2 cell lineage suggests that pTH-C is the only major source of thalamic nuclei containing neurons that project to the cerebral cortex, whereas pTH-R and ZLI are likely to produce distinct postmitotic populations outside of the cortex-projecting part of the thalamus. To determine if pTH-C is composed of subdomains, we characterized expression of the homeodomain protein Dbx1 and the bHLH protein Olig2. We show that Dbx1 is expressed in caudodorsal-high to rostroventral-low gradient within pTH-C. Analysis of heterozygous Dbx1(nlslacZ) knockin mice demonstrated that Dbx1-expressing progenitors preferentially give rise to caudodorsal thalamic nuclei. Olig2 is expressed in an opposite gradient within pTH-C to that of Dbx1. These results establish the molecular heterogeneity within the progenitor cells of the thalamus, and suggest that such heterogeneity contributes to the specification of thalamic nuclei.

Neurogenin1 expression in cell lineages of the cerebellar cortex in embryonic and postnatal mice

“…Ngn1 EGFP/þ mice have been used to map short-term cell fates in the developing thalamus (Vue et al, 2007) and co-immunolabeling of Ngn1 confirms the persistence of enhanced green fluorescent protein (EGFP) reporter in differentiating Ngn1…”

Transcriptional regulatory mechanisms underlying the GABAergic neuron fate in different diencephalic prosomeres

“…Together with the domain-specific transcription factors, Zliderived signals regulate the activity of proneural genes Ngn1 (Neurog1), Ngn2 (Neurog2) and Ascl1 in the neural progenitor cells of the ventricular zone (VZ) (Scholpp and Lumsden, 2010;Vue et al, 2007). These transcriptional networks are thought to regulate both cell-cycle exit and neuronal identity at the level of proliferative progenitor cells.…”

“…These transcriptional networks are thought to regulate both cell-cycle exit and neuronal identity at the level of proliferative progenitor cells. Ngn1 and Ngn2 are expressed in the progenitors of a large caudal domain of P2/thalamus (pTH-C), which gives rise to the thalamic glutamatergic neurons (Chen et al, 2009;Garcia-Lopez et al, 2004;Vue et al, 2007). In turn, Ascl1 is expressed in the progenitors of P3/prethalamus, P1/pretectum, and a narrow domain in the most rostral part of P2 (pTh-R; also called Rim, P2ZL) (Kataoka and Shimogori, 2008;Vue et al, 2007).…”

“…Ngn1 and Ngn2 are expressed in the progenitors of a large caudal domain of P2/thalamus (pTH-C), which gives rise to the thalamic glutamatergic neurons (Chen et al, 2009;Garcia-Lopez et al, 2004;Vue et al, 2007). In turn, Ascl1 is expressed in the progenitors of P3/prethalamus, P1/pretectum, and a narrow domain in the most rostral part of P2 (pTh-R; also called Rim, P2ZL) (Kataoka and Shimogori, 2008;Vue et al, 2007). Progenitors in P1 and pTh-R produce postmitotic neuronal precursors expressing genes encoding the GABAergic marker Gad1 and the transcription factors Tal1, Tal2 and Sox14 (Hashimoto-Torii et al, 2003;Kataoka and Shimogori, 2008).…”

“…Progenitors in P1 and pTh-R produce postmitotic neuronal precursors expressing genes encoding the GABAergic marker Gad1 and the transcription factors Tal1, Tal2 and Sox14 (Hashimoto-Torii et al, 2003;Kataoka and Shimogori, 2008). P1-derived precursors contribute to pretectal nuclei, whereas the pTh-R-derived precursors were recently shown to contribute to the IGL and vLGN (Jeong et al, 2011;Vue et al, 2007). In addition, vLGN has contributions from Zli and P3 (Delaunay et al, 2009;Kitamura et al, 1997;Suzuki-Hirano et al, 2011).…”