title: The transcription factor Foxg1 regulates telencephalic progenitor proliferation cell autonomously, in part by controlling Pax6 expression levels.
abstract: BACKGROUND
  The transcription factor Foxg1 is an important regulator of telencephalic cell cycles. Its inactivation causes premature lengthening of telencephalic progenitor cell cycles and increased neurogenic divisions, leading to severe hypoplasia of the telencephalon. These proliferation defects could be a secondary consequence of the loss of Foxg1 caused by the abnormal expression of several morphogens (Fibroblast growth factor 8, bone morphogenetic proteins) in the telencephalon of Foxg1 null mutants. Here we investigated whether Foxg1 has a cell autonomous role in the regulation of telencephalic progenitor proliferation. We analysed Foxg1+/+↔Foxg1-/- chimeras, in which mutant telencephalic cells have the potential to interact with, and to have any cell non-autonomous defects rescued by, normal wild-type cells.
  
  
  RESULTS
  Our analysis showed that the Foxg1-/- cells are under-represented in the chimeric telencephalon and the proportion of them in S-phase is significantly smaller than that of their wild-type neighbours, indicating that their under-representation is caused by a cell autonomous reduction in their proliferation. We then analysed the expression of the cell-cycle regulator Pax6 and found that it is cell-autonomously downregulated in Foxg1-/- dorsal telencephalic cells. We went on to show that the introduction into Foxg1-/- embryos of a transgene designed to reverse Pax6 expression defects resulted in a partial rescue of the telencephalic progenitor proliferation defects.
  
  
  CONCLUSIONS
  We conclude that Foxg1 exerts control over telencephalic progenitor proliferation by cell autonomous mechanisms that include the regulation of Pax6, which itself is known to regulate proliferation cell autonomously in a regional manner.
authors.affiliation: Genes and Development Group, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK. Martine.Manuel@ed.ac.uk
authors.forename: Martine N
authors.initials: MN
authors.lastname: Manuel
authors.forename: Ben
authors.initials: B
authors.lastname: Martynoga
authors.forename: Mike D
authors.initials: MD
authors.lastname: Molinek
authors.forename: Jane C
authors.initials: JC
authors.lastname: Quinn
authors.forename: Corinne
authors.initials: C
authors.lastname: Kroemmer
authors.forename: John O
authors.initials: JO
authors.lastname: Mason
authors.forename: David J
authors.initials: DJ
authors.lastname: Price
mesh_terms: D000818:Animals; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D002452:Cell Count; D049109:Cell Proliferation; D002678:Chimera; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D005136:Eye Proteins / Q000096:biosynthesis* / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000502:physiology*; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D011247:Pregnancy; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013687:Telencephalon / Q000166:cytology*
chemical_list: D000963:Antimetabolites; D005136:Eye Proteins; D051858:Forkhead Transcription Factors; C489565:Foxg1 protein, mouse; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D001973:Bromodeoxyuridine