Thyroid Hormone Signaling Acts as a Neurogenic Switch by Repressing Sox2 in the Adult Neural Stem Cell Niche
2012; Elsevier BV; Volume: 10; Issue: 5 Linguagem: Inglês
10.1016/j.stem.2012.04.008
ISSN1934-5909
AutoresAlejandra López‐Juárez, Sylvie Remaud, Zahra Hassani, Pascale Jolivet, Jacqueline Pierre Simons, Thomas Sontag, Kazuaki Yoshikawa, Jack Price, Ghislaine Morvan-Dubois, Barbara A. Demeneix,
Tópico(s)FOXO transcription factor regulation
ResumoThe subventricular zone (SVZ) neural stem cell niche contains mixed populations of stem cells, transit-amplifying cells, and migrating neuroblasts. Deciphering how endogenous signals, such as hormones, affect the balance between these cell types is essential for understanding the physiology of niche plasticity and homeostasis. We show that Thyroid Hormone (T3) and its receptor, TRα1, are directly involved in maintaining this balance. TRα1 is expressed in amplifying and migrating cells. In vivo gain- and loss-of-function experiments demonstrate first, that T3/TRα1 directly repress Sox2 expression, and second, that TRα1 overexpression in the niche favors the appearance of DCX+ migrating neuroblasts. Lack of TRα increases numbers of SOX2+ cells in the SVZ. Hypothyroidism increases proportions of cells in interphase. Thus, in the adult SVZ, T3/TRα1 together favor neural stem cell commitment and progression toward a migrating neuroblast phenotype; this transition correlates with T3/TRα1-dependent transcriptional repression of Sox2.
Referência(s)