INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
A neuronal Dll1 enhancer under positive selection in the lineage leading to anthropoids expanded reporter gene expression in the telencephalon of transgenic mice
Autor/es:
L. F. FRANCHINI, B. T. LAHN, M. RUBINSTEIN, R. LÓPEZ-LEAL
Lugar:
Chicago
Reunión:
Congreso; Society for Neuroscience; 2009
Resumen:
The neocortex, the most prominent structural and functional innovation of the mammalian brain, has expanded independently in several mammalian lineages. In anthropoid primates this expansion reached a maximum in the human lineage composing around 80 % of the entire brain mass. We hypothesize that uncovering the genetic basis of primate brain enlargement and functionality will shed light to understand human brain evolution. We have detected a highly conserved sequence showing signatures of rapid evolution in the lineage leading to anthropoids upstream of Delta-like 1 (Dll1), a gene involved in the proliferation/differentiation switch of neuronal precursors during brain development. Transgenic mouse studies showed that mouse and human orthologs of this conserved region are nervous system-specific enhancers active between E8.5 and E14.5 in the developing nervous system. Swapping the six anthropoid-specific nucleotides into the mouse enhancer produces an extension of the expression territory at E14.5 whereas swapping the ancestral nucleotides back into the human enhancer impaired proper expression of the reporter gene. These results indicate that positively selected substitutions in a neuronal Dll1 enhancer induced heterochronic gene expression that could have contributed to increase the number of neural precursors in the telencephalon of anthropoids and, ultimately, to shape a larger brain.