title: Pitx2c ensures habenular asymmetry by restricting parapineal cell number.
abstract: Left-right (L/R) asymmetries in the brain are thought to underlie lateralised cognitive functions. Understanding how neuroanatomical asymmetries are established has been achieved through the study of the zebrafish epithalamus. Morphological symmetry in the epithalamus is broken by leftward migration of the parapineal, which is required for the subsequent elaboration of left habenular identity; the habenular nuclei flank the midline and show L/R asymmetries in marker expression and connectivity. The Nodal target pitx2c is expressed in the left epithalamus, but nothing is known about its role during the establishment of asymmetry in the brain. We show that abrogating Pitx2c function leads to the right habenula adopting aspects of left character, and to an increase in parapineal cell numbers. Parapineal ablation in Pitx2c loss of function results in right habenular isomerism, indicating that the parapineal is required for the left character detected in the right habenula in this context. Partial parapineal ablation in the absence of Pitx2c, however, reduces the number of parapineal cells to wild-type levels and restores habenular asymmetry. We provide evidence suggesting that antagonism between Nodal and Pitx2c activities sets an upper limit on parapineal cell numbers. We conclude that restricting parapineal cell number is crucial for the correct elaboration of epithalamic asymmetry.
authors.affiliation: Université de Toulouse, UPS, Centre de Biologie du Développement (CBD), 118 route de Narbonne, F-31062 Toulouse, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Garric
authors.forename: Brice
authors.initials: B
authors.lastname: Ronsin
authors.forename: Myriam
authors.initials: M
authors.lastname: Roussigné
authors.forename: Sabrina
authors.initials: S
authors.lastname: Booton
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Gamse
authors.forename: Pascale
authors.initials: P
authors.lastname: Dufourcq
authors.forename: Patrick
authors.initials: P
authors.lastname: Blader
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000235:genetics*; D002452:Cell Count; D004625:Embryo, Nonmammalian; D019261:Epithalamus / Q000166:cytology / Q000196:embryology; D019262:Habenula / Q000166:cytology / Q000196:embryology*; D055457:Nodal Protein / Q000502:physiology; D009929:Organ Size / Q000235:genetics; D010870:Pineal Gland / Q000166:cytology / Q000196:embryology*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D055457:Nodal Protein; C572614:Pitx2 protein, zebrafish; D014157:Transcription Factors; D029961:Zebrafish Proteins
keywords: Epithalamus; Left-right; Nodal; Parapineal; Pitx2; Zebrafish