Foxa1 and Foxa2 are required for formation of the intervertebral discs.
PLoS One
; 8(1): e55528, 2013.
Article
en En
| MEDLINE
| ID: mdl-23383217
The intervertebral disc (IVD) is composed of 3 main structures, the collagenous annulus fibrosus (AF), which surrounds the gel-like nucleus pulposus (NP), and hyaline cartilage endplates, which are attached to the vertebral bodies. An IVD is located between each vertebral body. Degeneration of the IVD is thought to be a major cause of back pain, a potentially chronic condition for which there exist few effective treatments. The NP forms from the embryonic notochord. Foxa1 and Foxa2, transcription factors in the forkhead box family, are expressed early during notochord development. However, embryonic lethality and the absence of the notochord in Foxa2 null mice have precluded the study of potential roles these genes may play during IVD formation. Using a conditional Foxa2 allele in conjunction with a tamoxifen-inducible Cre allele (ShhcreER(T2)), we removed Foxa2 from the notochord of E7.5 mice null for Foxa1. Foxa1(-/-);Foxa2(c/c);ShhcreER(T2) double mutant animals had a severely deformed nucleus pulposus, an increase in cell death in the tail, decreased hedgehog signaling, defects in the notochord sheath, and aberrant dorsal-ventral patterning of the neural tube. Embryos lacking only Foxa1 or Foxa2 from the notochord were indistinguishable from control animals, demonstrating a functional redundancy for these genes in IVD formation. In addition, we provide in vivo genetic evidence that Foxa genes are required for activation of Shh in the notochord.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factor Nuclear 3-alfa del Hepatocito
/
Factor Nuclear 3-beta del Hepatocito
/
Disco Intervertebral
Límite:
Animals
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos