Repression of Fgf signaling by sprouty1-2 regulates cortical patterning in two distinct regions and times.
A fundamental question in developmental biology is how signaling pathways establish a transcription factor code that controls cell proliferation, regional fate and cell fate. Morphogenesis of the rostral telencephalon is controlled in part by Fgf signaling from the rostral patterning center. How Fgf signaling is regulated in the telencephalon is critical for understanding cerebral cortex formation. Here we show that mouse Sprouty1 and Sprouty2 (Spry1-2), which encode negative feedback regulators of Fgf signaling, are affecting cortical proliferation, differentiation, and the expression of genes regulating progenitor identity in the ventricular zone. In addition, Spry2 has a later function in regulating the MAPK pathway, proliferation, and gene expression in the cortex at mid-neurogenesis. Finally, we provide evidence that Coup-TFI, a transcription factor that promotes caudal fate, does so through repressing Fgf signaling, in part by promoting Spry expression.
Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco, San Francisco, California 94158-2611, USA. andrea.faedo@ucsf.edu
Andrea
A
Faedo
Ugo
U
Borello
John L R
JL
Rubenstein
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000201:enzymology / Q000502:physiology*; D002552:Cerebral Ventricles / Q000166:cytology / Q000196:embryology* / Q000201:enzymology / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013997:Time Factors
D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C425468:Spry1 protein, mouse; D005346:Fibroblast Growth Factors; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse