Expression of the guanine nucleotide exchange factor, mr-gef, is regulated during the differentiation of specific subsets of telencephalic neurons.
We have performed a screen combining subtractive hybridization with PCR to isolate genes that are regulated when neuroepithelial (NE) cells differentiate into neurons. From this screen, we have isolated a number of known genes that have not previously been associated with neurogenesis, together with several novel genes. Here we report that one of these genes, encoding a guanine nucleotide exchange factor (GEF), is regulated during the differentiation of distinct neuronal populations. We have cloned both rat and mouse GEF genes and shown that they are orthologs of the human gene, MR-GEF, which encodes a GEF that specifically activates the small GTPase, Rap1. We have therefore named the rat gene rat mr-gef (rmr-gef) and the mouse gene mouse mr-gef (mmr-gef). Here, we will collectively refer to these two rodent genes as mr-gef. Expression studies show that mr-gef is expressed by young neurons of the developing rodent CNS but not by progenitor cells in the ventricular zone (VZ). The expression pattern of mr-gef during early telencephalic neurogenesis is strikingly similar to that of GABA and the LIM homeobox gene Lhx6, a transcription factor expressed by GABAergic interneurons generated in the ventral telencephalon, some of which migrate into the cortex during development. These observations suggest that mr-gef encodes a protein that is part of a signaling pathway involved in telencephalic neurogenesis; particularly in the development of GABAergic interneurons.
Bithell
Angela
A
Section of Experimental Neuropathology and Psychiatry, Department of Psychological Medicine, The Institute of Psychiatry (P052), De Crespigny Park, London SE5 8AF, UK.
Alberta
John
J
Hornby
Fraser
F
Stiles
Charles D
CD
Williams
Brenda P
BP
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000032:analysis; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D060850:LIM-Homeodomain Proteins; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008168:Lung / Q000196:embryology / Q000378:metabolism; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000196:embryology / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D016133:Polymerase Chain Reaction / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D016415:Sequence Alignment; D013154:Spleen / Q000196:embryology / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D013737:Testis / Q000196:embryology / Q000378:metabolism; D014157:Transcription Factors; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000235:genetics / Q000378:metabolism; D020663:ras Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; D018398:Homeodomain Proteins; C121947:LHX6 protein, human; C498504:LHX6 protein, mouse; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D010982:Platelet-Derived Growth Factor; C417242:RAPGEF5 protein, human; D014157:Transcription Factors; D014404:Tubulin; C462941:beta3 tubulin, mouse; D020663:ras Guanine Nucleotide Exchange Factors; D005680:gamma-Aminobutyric Acid; D020932:Nerve Growth Factor