Dataset Information

Tcf7l2 is required for left-right asymmetric differentiation of habenular neurons.

ABSTRACT:

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.

SUBMITTER: Husken U

PROVIDER: S-EPMC4194317 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Publications

Tcf7l2 is required for left-right asymmetric differentiation of habenular neurons.

Hüsken Ulrike U Stickney Heather L HL Gestri Gaia G Bianco Isaac H IH Faro Ana A Young Rodrigo M RM Roussigne Myriam M Hawkins Thomas A TA Beretta Carlo A CA Brinkmann Irena I Paolini Alessio A Jacinto Raquel R Albadri Shahad S Dreosti Elena E Tsalavouta Matina M Schwarz Quenten Q Cavodeassi Florencia F Barth Anukampa K AK Wen Lu L Zhang Bo B Blader Patrick P Yaksi Emre E Poggi Lucia L Zigman Mihaela M Lin Shuo S Wilson Stephen W SW Carl Matthias M

Current biology : CB 20140904 19

<h4>Background</h4>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 ...[more]

PMID: 25201686

Similar Datasets

Project description:BackgroundNodal is an important determinant of the left-right (LR) body axis in bilaterians, specifying the right side in protostomes and non-chordate deuterostomes as opposed to the left side in chordates. Amphioxus represents an early-branching chordate group, rendering it especially useful for studying the character states that predate the origin of vertebrates. However, its anatomy, involving offset arrangement of axial structures, marked asymmetry of the oropharyngeal region, and, most notably, a mouth positioned on the left side, contrasts with the symmetric arrangement of the corresponding regions in other chordates.ResultsWe show that the Nodal signaling pathway acts to specify the LR axis in the cephalochordate amphioxus in a similar way as in vertebrates. At early neurula stages, Nodal switches from initial bilateral to the left-sided expression and subsequently specifies the left embryonic side. Perturbation of Nodal signaling with small chemical inhibitors (SB505124 and SB431542) alters expression of other members of the pathway and of left/right-sided, organ-specific genes. Upon inhibition, larvae display loss of the innate alternation of both somites and axons of peripheral nerves and loss of left-sided pharyngeal structures, such as the mouth, the preoral pit, and the duct of the club-shaped gland. Concomitantly, the left side displays ectopic expression of otherwise right-sided genes, and the larvae exhibit bilaterally symmetrical morphology, with duplicated endostyle and club-shaped gland structures.ConclusionsWe demonstrate that Nodal signaling is necessary for establishing the LR embryonic axis and for developing profound asymmetry in amphioxus. Our data suggest that initial symmetry breaking in amphioxus and propagation of the pathway on the left side correspond with the situation in vertebrates. However, the organs that become targets of the pathway differ between amphioxus and vertebrates, which may explain the pronounced asymmetry of its oropharyngeal and axial structures and the left-sided position of the mouth.

Dataset Information

Tcf7l2 is required for left-right asymmetric differentiation of habenular neurons.

Background

Results

Conclusions

Publications

Tcf7l2 is required for left-right asymmetric differentiation of habenular neurons.

Similar Datasets

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