I hypothesize that Fgf signaling from the rostral patterning center plays a major role in governing growth and patterning of the rostral telencephalon, including the frontal cortex. The experiments described below are designed to identify the molecular mechanisms that control: 1) Fgf expression and signaling;2) how Fgfs, and other signals, regulate expression of enhancers that drive expression in the developing frontal cortex;3) morphogenesis of the rostral telencephalon (frontal cortex and septum). The proposal has four Aims:
Aim I. Characterize the fates of cells in the rostral patterning center.
Aim II. Identify mechanisms that regulate gene expression in the rostral patterning center.
Aim III. Investigate the regulation of frontal cortex patterning: identify and characterize enhancers that define subdivisions of the frontal cortex.
Aim I V. Analyze roles of Fgf signal regulation in the rostral patterning center: analysis of Sprouty1, 2 and 1/2 mutants. I believe that these experiments will provide a firm foundation for elucidating the genetic, molecular, and cellular mechanisms that control development of the cerebral cortex and that may underlie some Human neurodevelopmental disorders such as Autism, Schizophrenia, and Epilepsy.
Disruption of cerebral cortex development and function is strongly associated with several major neuropsychiatric disorders, including autism and schizophrenia. The experiments proposed in this application aim to elucidate basic mechanisms that underlie normal development of prefrontal cortex, an integral region subserving higher cognitive function. This information will provide a key foundation for understanding the genetic and molecular mechanisms underlying many psychiatric disorders.
|Ypsilanti, Athéna R; Rubenstein, John L R (2016) Transcriptional and epigenetic mechanisms of early cortical development: An examination of how Pax6 coordinates cortical development. J Comp Neurol 524:609-29|
|Gobius, Ilan; Morcom, Laura; Suárez, Rodrigo et al. (2016) Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum. Cell Rep 17:735-747|
|Notwell, James H; Heavner, Whitney E; Darbandi, Siavash Fazel et al. (2016) TBR1 regulates autism risk genes in the developing neocortex. Genome Res 26:1013-22|
|Nord, Alex S; Pattabiraman, Kartik; Visel, Axel et al. (2015) Genomic perspectives of transcriptional regulation in forebrain development. Neuron 85:27-47|
|Prochazka, Jan; Prochazkova, Michaela; Du, Wen et al. (2015) Migration of Founder Epithelial Cells Drives Proper Molar Tooth Positioning and Morphogenesis. Dev Cell 35:713-24|
|Hoch, Renée V; Clarke, Jeffrey A; Rubenstein, John L R (2015) Fgf signaling controls the telencephalic distribution of Fgf-expressing progenitors generated in the rostral patterning center. Neural Dev 10:8|
|Hoch, Renée V; Lindtner, Susan; Price, James D et al. (2015) OTX2 Transcription Factor Controls Regional Patterning within the Medial Ganglionic Eminence and Regional Identity of the Septum. Cell Rep 12:482-94|
|Golonzhka, Olga; Nord, Alex; Tang, Paul L F et al. (2015) Pbx Regulates Patterning of the Cerebral Cortex in Progenitors and Postmitotic Neurons. Neuron 88:1192-207|
|Eckler, Matthew J; Nguyen, Ton D; McKenna, William L et al. (2015) Cux2-positive radial glial cells generate diverse subtypes of neocortical projection neurons and macroglia. Neuron 86:1100-1108|
|Parchem, Ronald J; Moore, Nicole; Fish, Jennifer L et al. (2015) miR-302 Is Required for Timing of Neural Differentiation, Neural Tube Closure, and Embryonic Viability. Cell Rep 12:760-73|
Showing the most recent 10 out of 57 publications