PUBLICATION
Tcf7l2 Is Required for Left-Right Asymmetric Differentiation of Habenular Neurons
- Authors
- Hüsken, U., Stickney, H.L., Gestri, G., Bianco, I.H., Faro, A., Young, R.M., Roussigne, M., Hawkins, T.A., Beretta, C.A., Brinkmann, I., Paolini, A., Jacinto, R., Albadri, S., Dreosti, E., Tsalavouta, M., Schwarz, Q., Cavodeassi, F., Barth, A.K., Wen, L., Zhang, B., Blader, P., Yaksi, E., Poggi, L., Zigman, M., Lin, S., Wilson, S.W., Carl, M.
- ID
- ZDB-PUB-140910-4
- Date
- 2014
- Source
- Current biology : CB 24(19): 2217-27 (Journal)
- Registered Authors
- Albadri, Shahad, Barth, Anukampa, Beretta, Carlo, Bianco, Isaac, Blader, Patrick, Carl, Matthias, Cavodeassi, Florencia, Dreosti, Elena, Faro, Ana, Gestri, Gaia, Hawkins, Tom, Lin, Shuo, Paolini, Alessio, Poggi, Lucia, Stickney, Heather, Wilson, Steve, Yaksi, Emre, Young, Rodrigo, Zhang, Bo, Zigman, Mihaela
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Differentiation*
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/physiology
- Gene Expression Regulation
- Habenula/cytology
- Habenula/embryology*
- Neurons/cytology
- Neurons/physiology*
- Signal Transduction
- Transcription Factor 7-Like 2 Protein/genetics*
- Transcription Factor 7-Like 2 Protein/metabolism
- Zebrafish/embryology*
- Zebrafish/physiology
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 25201686 Full text @ Curr. Biol.
Citation
Hüsken, U., Stickney, H.L., Gestri, G., Bianco, I.H., Faro, A., Young, R.M., Roussigne, M., Hawkins, T.A., Beretta, C.A., Brinkmann, I., Paolini, A., Jacinto, R., Albadri, S., Dreosti, E., Tsalavouta, M., Schwarz, Q., Cavodeassi, F., Barth, A.K., Wen, L., Zhang, B., Blader, P., Yaksi, E., Poggi, L., Zigman, M., Lin, S., Wilson, S.W., Carl, M. (2014) Tcf7l2 Is Required for Left-Right Asymmetric Differentiation of Habenular Neurons. Current biology : CB. 24(19):2217-27.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping