title: Wls provides a new compartmental view of the rhombic lip in mouse cerebellar development.
abstract: Math1 is the defining molecule of the cerebellar rhombic lip and Pax6 is downstream in the Math1 pathway. In the present study, we discover that Wntless (Wls) is a novel molecular marker of the cells in the interior face of the rhombic lip throughout normal mouse cerebellar development. Wls expression is found complementary to the expression of Math1 and Pax6, which are localized to the exterior face of the rhombic lip. To determine the interaction between these molecules, we examine the loss-of-Math1 or loss-of-Pax6 in the cerebellum, i.e., the Math1-null and Pax6-null (Sey) mutant cerebella. The presence of Wls-positive cells in the Math1-null rhombic lip indicates that Wls expression is independent of Math1. In the Sey mutant cerebellum, there is an expansion of Wls-expressing cells into regions that are normally colonized by Pax6-expressing cells. The ectopic expression of Wls in the Pax6-null cerebellum suggests a negative interaction between Wls-expressing cells and Pax6-positive cells. These findings suggest that the rhombic lip is dynamically patterned by the expression of Wls, Math1, and Pax6. We also examine five rhombic lip cell markers (Wls, Math1, Pax6, Lmx1a, and Tbr2) to identify four molecularly distinct compartments in the rhombic lip during cerebellar development. The existence of spatial compartmentation in the rhombic lip and the interplay between Wls, Math1, and Pax6 in the rhombic lip provides novel views of early cerebellar development.
authors.affiliation: Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z4H4 and.
authors.forename: Joanna
authors.identifier: http://orcid.org/0000-0003-0551-5305
authors.initials: J
authors.lastname: Yeung
authors.affiliation: Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z4H4 and.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Ha
authors.affiliation: Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z4H4 and.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Swanson
authors.affiliation: Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z4H4 and.
authors.forename: Kunho
authors.initials: K
authors.lastname: Choi
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Yiai
authors.initials: Y
authors.lastname: Tong
authors.affiliation: Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z4H4 and Dang@cmmt.ubc.ca.
authors.forename: Dan
authors.initials: D
authors.lastname: Goldowitz
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D019521:Body Patterning / Q000502:physiology*; D002531:Cerebellum / Q000196:embryology* / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins; C500943:Atoh1 protein, mouse; C545200:Gpr177 protein, mouse; C000605732:Pax6 protein, mouse
keywords: Pax6; Wls; cerebellar compartments; cerebellum; developmental biology; rhombic lip