Details

Autor(en) / Beteiligte

• Hüsken, Ulrike
• Stickney, Heather L.
• Gestri, Gaia
• Bianco, Isaac H.
• Faro, Ana
• Young, Rodrigo M.
• Roussigne, Myriam
• Hawkins, Thomas A.
• Beretta, Carlo A.
• Brinkmann, Irena
• Paolini, Alessio
• Jacinto, Raquel
• Albadri, Shahad
• Dreosti, Elena
• Tsalavouta, Matina
• Schwarz, Quenten
• Cavodeassi, Florencia
• Barth, Anukampa K.
• Wen, Lu
• Zhang, Bo
• Blader, Patrick
• Yaksi, Emre
• Poggi, Lucia
• Zigman, Mihaela
• Lin, Shuo
• Wilson, Stephen W.
• Carl, Matthias

Titel

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

Ist Teil von

• Current biology, 2014-10, Vol.24 (19), p.2217-2227

Ort / Verlag

England: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. 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. Tcf7l2 is essential for lateralized fate selection by habenular neurons that can differentiate along two alternative pathways, thereby leading to major neural circuit asymmetries. •Zebrafish with mutations in tcf7l2 lose left-right asymmetries in habenular neurons•Tcf7l2 is expressed in both left and right-sided habenular neurons•Tcf7l2 enables neurons to respond to signals that differ between left and right Although left-right asymmetries are common features of nervous systems, their developmental bases are largely unknown. This study in zebrafish by Hüsken et al. reveals that Tcf7l2 is essential for lateralized fate selection by neurons that can differentiate along two alternative pathways, thereby leading to major neural circuit asymmetries.