title: Effects of Emx2 inactivation on the gene expression profile of neural precursors.
abstract: Emx2 plays a crucial role in the development of the diencephalon and dorsal telencephalon. Thus, Emx2-null mutants have abnormal cortical lamination and a reduction in size of the caudal and medial areas of the prosencephalon. Emx2 is expressed in neural precursors of the subventricular zone in vivo and in cultured neurospheres in vitro where it controls the size of the transit-amplifying population, affecting proliferation and clonal efficiency of neural stem cells. To identify the cellular processes mastered by Emx2, and possibly the molecular mechanisms by which the gene exerts its action, we compared the expression profile of cultured neurospheres derived from wild-type and Emx2-null mouse embryos. The differential expression of several genes was also confirmed by semiquantitative RT-PCR, real-time PCR and cytofluorimetric analysis in different preparations of neurospheres, and by in situ hybridization. The gene expression profile suggested a role for Emx2 in regulating the differentiation and migration properties of neural precursor cells. This involvement was confirmed in vitro, where the altered clonogenicity and impaired migration of Emx2-null cells were partially corrected by transduction of the Emx2 gene. Taken together, our results indicate that Emx2 is indeed involved in the transition between resident early progenitors (perhaps stem cells) and more mature precursors capable of migrating out of the ventricular zone, becoming postmitotic and differentiating into the appropriate cell type, and help explain the alterations observed in the brains of knock-out mice.
authors.affiliation: National Institute for Cancer Research, 16132 Genova, Italy.
authors.forename: Rosaria M R
authors.initials: RM
authors.lastname: Gangemi
authors.forename: Antonio
authors.initials: A
authors.lastname: Daga
authors.forename: Luca
authors.initials: L
authors.lastname: Muzio
authors.forename: Daniela
authors.initials: D
authors.lastname: Marubbi
authors.forename: Serena
authors.initials: S
authors.lastname: Cocozza
authors.forename: Marzia
authors.initials: M
authors.lastname: Perera
authors.forename: Sara
authors.initials: S
authors.lastname: Verardo
authors.forename: Domenico
authors.initials: D
authors.lastname: Bordo
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Griffero
authors.forename: Maria C
authors.initials: MC
authors.lastname: Capra
authors.forename: Antonello
authors.initials: A
authors.lastname: Mallamaci
authors.forename: Giorgio
authors.initials: G
authors.lastname: Corte
mesh_terms: D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D001921:Brain / Q000166:cytology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis / Q000379:methods; D009474:Neurons / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013234:Stem Cells / Q000502:physiology*; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D018398:Homeodomain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins