title: Hindbrain rhombic lip is comprised of discrete progenitor cell populations allocated by Pax6.
abstract: The lower rhombic lip (LRL) is a germinal zone in the dorsal hindbrain productive of tangentially migrating neurons, streaming extramurally (mossy fiber neurons) or intramurally (climbing fiber neurons). Here we show that LRL territory, operationally defined by Wnt1 expression, is parceled into molecular subdomains predictive of cell fate. Progressing dorsoventrally, Lmx1a and Gdf7 expression identifies the primordium for hindbrain choroid plexus epithelial cells; Math1, for mossy fiber neurons; and immediately ventral to Math1 yet within Wnt1(+) territory, a climbing fiber primordium dominated by Ngn1-expressing cells. Elimination of Pax6 results in expansion of this Ngn1(+) progenitor pool and reduction in the Math1(+) pool, with accompanying later enlargement of the climbing fiber nucleus and reductions in mossy fiber nuclei. Pax6 loss also disrupts Msx expression cell-nonautonomously, suggesting Pax6 may influence LRL progenitor identity indirectly through potentiating BMP signaling. These studies suggest that underlying the diversity and proportions of fates produced by the LRL is a precise suborganization regulated by Pax6.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Landsberg
authors.forename: Rajeshwar B
authors.initials: RB
authors.lastname: Awatramani
authors.forename: Nina L
authors.initials: NL
authors.lastname: Hunter
authors.forename: Anna F
authors.initials: AF
authors.lastname: Farago
authors.forename: Heather J
authors.initials: HJ
authors.lastname: DiPietrantonio
authors.forename: Carolyn I
authors.initials: CI
authors.lastname: Rodriguez
authors.forename: Susan M
authors.initials: SM
authors.lastname: Dymecki
mesh_terms: D000344:Afferent Pathways / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D019521:Body Patterning / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002531:Cerebellum / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002831:Choroid Plexus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D055412:Growth Differentiation Factors; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008822:Mice, Transgenic; D009412:Nerve Fibers / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009847:Olivary Nucleus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019485:Bone Morphogenetic Proteins; D005136:Eye Proteins; D055412:Growth Differentiation Factors; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D051155:Wnt1 Protein; C500943:Atoh1 protein, mouse; C499471:Gdf7 protein, mouse; C489692:Lmx1a protein, mouse; C000605732:Pax6 protein, mouse; C495246:Wnt1 protein, mouse; C486336:Neurog1 protein, mouse