Distinct temporal requirements for the homeobox gene Gsx2 in specifying striatal and olfactory bulb neuronal fates.
The homeobox gene Gsx2 (formerly Gsh2) is known to be required for striatal and olfactory bulb neurogenesis; however, its specific role in the specification of these two neuronal subtypes remains unclear. To address this, we have employed a temporally regulated gain-of-function approach in transgenic mice and found that misexpression of Gsx2 at early stages of telencephalic neurogenesis favors the specification of striatal projection neuron identity over that of olfactory bulb interneurons. In contrast, delayed activation of the Gsx2 transgene until later stages exclusively promotes olfactory bulb interneuron identity. In a complementary approach, we have conditionally inactivated Gsx2 in a temporally progressive manner. Unlike germline Gsx2 mutants, which exhibit severe alterations in both striatal and olfactory bulb neurogenesis at birth, the conditional mutants exhibited defects restricted to olfactory bulb interneurons. These results demonstrate that Gsx2 specifies striatal projection neuron and olfactory bulb interneuron identity at distinct time points during telencephalic neurogenesis.
Waclaw
Ronald R
RR
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Wang
Bei
B
Pei
Zhenglei
Z
Ehrman
Lisa A
LA
Campbell
Kenneth
K
D000818:Animals; D003342:Corpus Striatum / Q000196:embryology / Q000473:pathology*; D005260:Female; D005801:Genes, Homeobox / Q000502:physiology*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D007395:Interneurons / Q000473:pathology* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D055495:Neurogenesis / Q000235:genetics*; D009830:Olfactory Bulb / Q000196:embryology / Q000473:pathology*; D011247:Pregnancy; D013997:Time Factors
C109498:Gsh2 protein, mouse; D018398:Homeodomain Proteins