Ascl1 Participates in Cajal-Retzius Cell Development in the Neocortex

作者：Dixit Rajiv; Zimmer Celine; Waclaw Ronald R; Mattar Pierre; Shaker Tarek; Kovach Christopher; Logan Cairine; Campbell Kenneth; Guillemot Francois; Schuurmans Carol^*

来源：Cerebral Cortex, 2011, 21(11): 2599-2611.

DOI：10.1093/cercor/bhr046

• basic-helix-loop-helix
• dorsal telencephalon
• pallium
• proneural gene
• transcription factor

Cajal-Retzius cells are essential pioneer neurons that guide neuronal migration in the developing neocortex. During development, Cajal-Retzius cells arise from distinct progenitor domains that line the margins of the dorsal telencephalon, or pallium. Here, we show that the proneural gene Ascl1 is expressed in Cajal-Retzius cell progenitors in the pallial septum, ventral pallium, and cortical hem. Using a short-term lineage trace, we demonstrate that it is primarily the Ascl1-expressing progenitors in the pallial septum and ventral pallium that differentiate into Cajal-Retzius cells. Accordingly, we found a small, albeit significant reduction in the number of Reelin(+) and Trp73(+) Cajal-Retzius cells in the Ascl1(-/-) neocortex. Conversely, using a gain-of-function approach, we found that Ascl1 induces the expression of both Reelin, a Cajal-Retzius marker, and Tbr1, a marker of pallial-derived neurons, in a subset of early-stage pallial progenitors, an activity that declines over developmental time. Taken together, our data indicate that the proneural gene Ascl1 is required and sufficient to promote the differentiation of a subset of Cajal-Retzius neurons during early neocortical development. Notably, this is the first study that reports a function for Ascl1 in the pallium, as this gene is best known for its role in specifying subpallial neuronal identities.

• 出版日期2011-11
• 单位河北医科大学