The cerebral cortex is essential for higher cognitive functions of the mammalian brain. Anatomically distinct regions within the cortex are responsible for processing distinct functions. For instance, different domains of the cortex process different sensory inputs (i.e. vision, hearing, olfaction and somatosensation). Little is known about the developmental and genetic mechanisms that control parcellation of the cortex into these areas. I hypothesize that regionalization of the cerebral cortex is regulated by the expression of secreted molecules, such as Fgf8, by midline patterning centers of the embryonic telencephalon. These molecules may control regionalization through generating gradiential expression of transcription factors. The experiments proposed herein will explore the role of FGF8, and selected transcription factors whose expression appears to be controlled by FGF8, in regulating anteroposterior patterning of the cerebral cortex. These studies will have implications for understanding human disorders that range from gross malformations of the forebrain to dysfunction of individual subdivisions of the cerebral cortex.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034661-07
Application #
6710046
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Gwinn, Katrina
Project Start
1996-09-01
Project End
2006-02-28
Budget Start
2004-03-01
Budget End
2005-02-28
Support Year
7
Fiscal Year
2004
Total Cost
$287,850
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Dickel, Diane E; Ypsilanti, Athena R; Pla, Ramón et al. (2018) Ultraconserved Enhancers Are Required for Normal Development. Cell 172:491-499.e15
Fazel Darbandi, Siavash; Robinson Schwartz, Sarah E; Qi, Qihao et al. (2018) Neonatal Tbr1 Dosage Controls Cortical Layer 6 Connectivity. Neuron 100:831-845.e7
Liu, Jinyue; Reggiani, Jasmine D S; Laboulaye, Mallory A et al. (2018) Tbr1 instructs laminar patterning of retinal ganglion cell dendrites. Nat Neurosci 21:659-670
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; 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
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

Showing the most recent 10 out of 60 publications