The CRE/CREB pathway is transiently expressed in thalamic circuit development and contributes to refinement of retinogeniculate axons.
The development of precise connections in the mammalian brain proceeds through refinement of initially diffuse patterns, a process that occurs largely within critical developmental windows. To elucidate the molecular pathways that orchestrate these early periods of circuit remodeling, we have examined the role of a calcium- and cAMP-regulated transcriptional pathway. We show that there is a window of CRE/CREB-mediated gene expression in the developing thalamus, which precedes neocortical expression. In the LGN, this wave of gene expression occurs prior to visual experience, but requires retinal function. Mutant mice with reduced CREB expression show loss of refinement of retinogeniculate projections. These results suggest an important role of the CRE/CREB transcriptional pathway in the coordination of experience-independent circuit remodeling during forebrain development.
Pham
T A
TA
Department of Psychiatry and Behavioral Sciences, Graduate Program in Neurobiology and Behavior, University of Washington School of Medicine, Seattle, WA 98195, USA. tonypham@u.washington.edu
Rubenstein
J L
JL
Silva
A J
AJ
Storm
D R
DR
Stryker
M P
MP
D000375:Aging; D000818:Animals; D001369:Axons / Q000502:physiology*; D003433:Crosses, Genetic; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D015353:Eye Enucleation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005829:Geniculate Bodies / Q000502:physiology*; D006579:Heterozygote; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012160:Retina / Q000502:physiology*; D013788:Thalamus / Q000254:growth & development / Q000502:physiology*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014795:Visual Pathways / Q000502:physiology*; D001616:beta-Galactosidase / Q000235:genetics
D017362:Cyclic AMP Response Element-Binding Protein; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases; D001616:beta-Galactosidase