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Article Dans Une Revue Current Biology - CB Année : 2014

Tcf7l2 Is Required for Left-Right Asymmetric Differentiation of Habenular Neurons

Myriam Roussigné
Carlo a. Beretta
  • Fonction : Auteur
Irena Brinkmann
  • Fonction : Auteur
Alessio Paolini
  • Fonction : Auteur
Raquel Jacinto
  • Fonction : Auteur
Shahad Albadri
Elena Dreosti
  • Fonction : Auteur
Matina Tsalavouta
  • Fonction : Auteur
Quenten Schwarz
  • Fonction : Auteur
Florencia Cavodeassi
  • Fonction : Auteur
Anukampa k. Barth
  • Fonction : Auteur
Lu Wen
  • Fonction : Auteur
Bo Zhang
  • Fonction : Auteur
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Patrick Blader
Emre Yaksi
  • Fonction : Auteur
Lucia Poggi
  • Fonction : Auteur
Mihaela Zigman
  • Fonction : Auteur
Shuo Lin
  • Fonction : Auteur
Stephen w. Wilson
  • Fonction : Auteur

Résumé

Background: Although left-right asymmetries are common features of nervous systems, their developmental bases are largely unknown. In the zebrafish epithalamus, dorsal habenular neurons adopt medial (dHbm) and lateral (dHbl) subnuclear character at very different frequencies on the left and right sides. The left-sided parapineal promotes the elaboration of dHbl character in the left habenula, albeit by an unknown mechanism. Likewise, the genetic pathways acting within habenular neurons to control their asymmetric differentiated character are unknown. Results: In a forward genetic screen for mutations that result in loss of habenular asymmetry, we identified two mutant alleles of tcf7l2, a gene that encodes a transcriptional regulator of Wnt signaling. In tcf7l2 mutants, most neurons on both sides differentiate with dHbl identity. Consequently, the habenulae develop symmetrically, with both sides adopting a pronounced leftward character. Tcf7l2 acts cell automously in nascent equipotential neurons, and on the right side, it promotes dHbm and suppresses dHbl differentiation. On the left, the parapineal prevents this Tcf7l2-dependent process, thereby promoting dHbl differentiation. Conclusions: Tcf7l2 is essential for lateralized fate selection by habenular neurons that can differentiate along two alternative pathways, thereby leading to major neural circuit asymmetries.
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Dates et versions

hal-03043901 , version 1 (07-12-2020)

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Ulrike Hüsken, Heather L Stickney, Gaia Gestri, Isaac H Bianco, Ana Faro, et al.. Tcf7l2 Is Required for Left-Right Asymmetric Differentiation of Habenular Neurons. Current Biology - CB, 2014, 24 (19), pp.2217-2227. ⟨10.1016/j.cub.2014.08.006⟩. ⟨hal-03043901⟩
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