Cis-regulatory control of corticospinal system development and evolution.
Nature
; 486(7401): 74-9, 2012 May 30.
Article
en En
| MEDLINE
| ID: mdl-22678282
ABSTRACT
The co-emergence of a six-layered cerebral neocortex and its corticospinal output system is one of the evolutionary hallmarks of mammals. However, the genetic programs that underlie their development and evolution remain poorly understood. Here we identify a conserved non-exonic element (E4) that acts as a cortex-specific enhancer for the nearby gene Fezf2 (also known as Fezl and Zfp312), which is required for the specification of corticospinal neuron identity and connectivity. We find that SOX4 and SOX11 functionally compete with the repressor SOX5 in the transactivation of E4. Cortex-specific double deletion of Sox4 and Sox11 leads to the loss of Fezf2 expression, failed specification of corticospinal neurons and, independent of Fezf2, a reeler-like inversion of layers. We show evidence supporting the emergence of functional SOX-binding sites in E4 during tetrapod evolution, and their subsequent stabilization in mammals and possibly amniotes. These findings reveal that SOX transcription factors converge onto a cis-acting element of Fezf2 and form critical components of a regulatory network controlling the identity and connectivity of corticospinal neurons.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Médula Espinal
/
Elementos de Facilitación Genéticos
/
Regulación del Desarrollo de la Expresión Génica
/
Evolución Molecular
/
Neocórtex
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Nature
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos