title: Pleiotropic and isoform-specific functions for Pitx2 in superior colliculus and hypothalamic neuronal development.
abstract: Transcriptional regulation of gene expression during development is critical for proper neuronal differentiation and migration. Alternative splicing and differential isoform expression have been demonstrated for most mammalian genes, but their specific contributions to gene function are not well understood. In mice, the transcription factor gene Pitx2 is expressed as three different isoforms (PITX2A, PITX2B, and PITX2C) which have unique amino termini and common DNA binding homeodomains and carboxyl termini. The specific roles of these isoforms in neuronal development are not known. Here we report the onset of Pitx2ab and Pitx2c isoform-specific expression by E9.5 in the developing mouse brain. Using isoform-specific Pitx2 deletion mouse strains, we show that collicular neuron migration requires PITX2AB and that collicular GABAergic differentiation and targeting of hypothalamic projections require unique Pitx2 isoform dosage. These results provide insights into Pitx2 dosage and isoform-specific requirements underlying midbrain and hypothalamic development.
authors.affiliation: Cellular and Molecular Biology Graduate Program, 2966 Taubman Medical Library, University of Michigan, Ann Arbor, MI 48109-0619, USA. mrwaite@umich.edu
authors.forename: Mindy R
authors.initials: MR
authors.lastname: Waite
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Skidmore
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Micucci
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Shiratori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamada
authors.forename: James F
authors.initials: JF
authors.lastname: Martin
authors.forename: Donna M
authors.initials: DM
authors.lastname: Martin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000196:embryology* / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013477:Superior Colliculi / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000097577:Homeobox Protein PITX2
chemical_list: D018398:Homeodomain Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2