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The Journal of Neuroscience, October 10, 2007, 27(41):11103-11111; doi:10.1523/JNEUROSCI.1066-07.2007

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Development/Plasticity/Repair
The Role of Foxg1 and Dorsal Midline Signaling in the Generation of Cajal-Retzius Subtypes

Carina Hanashima,¹ Marie Fernandes,² Jean M. Hebert,² and Gord Fishell¹

¹Smilow Neuroscience Program and Department of Cell Biology, Smilow Research Center, New York University, New York, New York 10016, and ²Departments of Neuroscience and Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461

Correspondence should be addressed to Gord Fishell, Smilow Neuroscience Program and Department of Cell Biology, Fifth Floor, Smilow Research Center, New York University, 522 First Avenue, New York, NY 10016. Email: fishell{at}saturn.med.nyu.edu

Cajal-Retzius (CR) cells, the earliest-born neurons in the neocortex, arise from discrete sources within the telencephalon, including the dorsal midline and the pallial–subpallial boundary (PSB). In particular, the cortical hem, a region of high bone morphogenetic proteins (BMPs) and Wnt (wingless-type MMTV integration site family) expression but lacking in Foxg1 (forkhead box G1) is a major source of CR neurons. Whether CR cells from distinct origins arise from disparate developmental processes or share a common mechanism is unclear. To elucidate the molecular basis of CR cell development, we assessed the role of both Foxg1 and dorsal midline signaling in the production of cortical hem- and PSB-derived CR cells. We demonstrate that the loss of Foxg1 results in the overproduction of both of these CR populations. However, removal of Foxg1 at embryonic day 13, although expanding the number of CR cells with a PSB phenotype, does not result in an expansion of BMPs or Wnts in the dorsomedial signaling center. Conversely, loss of the dorsal midline ligands as observed in Gli3 (glioma-associated oncogene homolog 3) mutants results in the loss of the cortical hem-derived CR character but does not affect the specification of PSB-derived CR cells. Hence, our findings demonstrate that, although the specification of cortical hem-derived CR cells is dependent on signaling from the dorsal midline, Foxg1 functions to repress the generation of both cortical hem- and PSB-derived CR cells.

Key words: Foxg1; Cajal-Retzius cells; dorsal midline; pallial–subpallial boundary; BMPs; telencephalon

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Received Dec. 12, 2006; revised Aug. 17, 2007; accepted Aug. 20, 2007.

Correspondence should be addressed to Gord Fishell, Smilow Neuroscience Program and Department of Cell Biology, Fifth Floor, Smilow Research Center, New York University, 522 First Avenue, New York, NY 10016. Email: fishell{at}saturn.med.nyu.edu

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