title: Ascl1 participates in Cajal-Retzius cell development in the neocortex.
abstract: 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.
authors.affiliation: Hotchkiss Brain Institute, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Dixit
authors.forename: Céline
authors.initials: C
authors.lastname: Zimmer
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Waclaw
authors.forename: Pierre
authors.initials: P
authors.lastname: Mattar
authors.forename: Tarek
authors.initials: T
authors.lastname: Shaker
authors.forename: Christopher
authors.initials: C
authors.lastname: Kovach
authors.forename: Cairine
authors.initials: C
authors.lastname: Logan
authors.forename: Kenneth
authors.initials: K
authors.lastname: Campbell
authors.forename: François
authors.initials: F
authors.lastname: Guillemot
authors.forename: Carol
authors.initials: C
authors.lastname: Schuurmans
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D019579:Neocortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D000091042:Reelin Protein
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000091042:Reelin Protein; C499317:Ascl1 protein, mouse; C000717128:Reln protein, mouse