title: Msx1-Positive Progenitors in the Retinal Ciliary Margin Give Rise to Both Neural and Non-neural Progenies in Mammals.
abstract: In lower vertebrates, stem/progenitor cells located in a peripheral domain of the retina, called the ciliary margin zone (CMZ), cooperate with retinal domain progenitors to build the mature neural retina. In mammals, it is believed that the CMZ lacks neurogenic potential and that the retina develops from one pool of multipotent retinal progenitor cells (RPCs). Here we identify a population of Msx1-expressing progenitors in the mouse CMZ that is both molecularly and functionally distinct from RPCs. Using genetic lineage tracing, we report that Msx1 progenitors have unique developmental properties compared with RPCs. Msx1 lineages contain both neural retina and non-neural ciliary epithelial progenies and overall generate fewer photoreceptors than classical RPC lineages. Furthermore, we show that the endocytic adaptor protein Numb regulates the balance between neural and non-neural fates in Msx1 progenitors. These results uncover a population of CMZ progenitors, distinct from classical RPCs, that also contributes to mammalian retinogenesis.
authors.affiliation: Cellular Neurobiology Research Unit, Institut de recherches cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada; Division of Experimental Medicine, McGill University, Montreal, QC H3A 1A3, Canada.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Bélanger
authors.affiliation: Department of Molecular Genetics of Morphogenesis, Institut Pasteur, Paris 75015, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Robert
authors.affiliation: Cellular Neurobiology Research Unit, Institut de recherches cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada; Division of Experimental Medicine, McGill University, Montreal, QC H3A 1A3, Canada; Department of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada. Electronic address: michel.cayouette@ircm.qc.ca.
authors.forename: Michel
authors.initials: M
authors.lastname: Cayouette
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D060049:Asymmetric Cell Division; D019070:Cell Lineage; D049109:Cell Proliferation; D002923:Cilia / Q000378:metabolism*; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D005260:Female; D019426:Integrases / Q000378:metabolism; D051957:MSX1 Transcription Factor / Q000378:metabolism*; D008322:Mammals / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010858:Pigmentation; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D051957:MSX1 Transcription Factor; D008565:Membrane Proteins; C484084:Msx1 protein, mouse; D009419:Nerve Tissue Proteins; C106293:Numb protein, mouse; C045073:Cre recombinase; D019426:Integrases
keywords: Msx1; Numb; ciliary margin; conditional knockout; fate decision; lineage; mouse genetics; neurogenesis; retina; stem cell