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The Corticofugal Neuron-Associated Genes ROBO1, SRGAP1, and CTIP2 Exhibit an Anterior to Posterior Gradient of Expression in Early Fetal Human Neocortex Development

Lookup NU author(s): Bui Ip, Dr Nadhim Bayatti, Professor Susan Lindsay, Dr Gavin Clowry

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Abstract

Developing neocortical progenitors express transcription factors in gradients that induce programs of region-specific gene expression. Our previous work identified anteriorly upregulated expression gradients of a number of corticofugal neuron-associated gene probe sets along the anterior-posterior axis of the human neocortex (8-12 postconceptional weeks [PCW]). Here, we demonstrate by real-time polymerase chain reaction, in situ hybridization and immunohistochemistry that 3 such genes, ROBO1, SRGAP1, and CTIP2 are highly expressed anteriorly between 8-12 PCW, in comparison with other genes (FEZF2, SOX5) expressed by Layer V, VI, and subplate neurons. All 3 were prominently expressed by early postmitotic neurons in the subventricular zone, intermediate zone, and cortical plate (CP) from 8 to 10 PCW. Between 12 and 15 PCW expression patterns for ER81 and SATB2 (Layer V), TBR1 (Layer V/VI) and NURR1 (Layer VI) revealed Layer V forming. By 15 PCW, ROBO1 and SRGAP1 expression was confined to Layer V, whereas CTIP2 was expressed throughout the CP anteriorly. We observed ROBO1 and SRGAP1 immunoreactivity in medullary corticospinal axons from 11 PCW onward. Thus, we propose that the coexpression of these 3 markers in the anterior neocortex may mark the early location of the human motor cortex, including its corticospinal projection neurons, allowing further study of their early differentiation.


Publication metadata

Author(s): Ip BK, Bayatti N, Howard NJ, Lindsay S, Clowry GJ

Publication type: Article

Publication status: Published

Journal: Cerebral Cortex

Year: 2011

Volume: 21

Issue: 6

Pages: 1395-1407

Print publication date: 08/11/2011

ISSN (print): 1047-3211

ISSN (electronic): 1460-2199

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/cercor/bhq219

DOI: 10.1093/cercor/bhq219


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