Functional differentiation of a clone resembling embryonic cortical interneuron progenitors.
We have generated clones (L2.3 and RG3.6) of neural progenitors with radial glial properties from rat E14.5 cortex that differentiate into astrocytes, neurons, and oligodendrocytes. Here, we describe a different clone (L2.2) that gives rise exclusively to neurons, but not to glia. Neuronal differentiation of L2.2 cells was inhibited by bone morphogenic protein 2 (BMP2) and enhanced by Sonic Hedgehog (SHH) similar to cortical interneuron progenitors. Compared with L2.3, differentiating L2.2 cells expressed significantly higher levels of mRNAs for glutamate decarboxylases (GADs), DLX transcription factors, calretinin, calbindin, neuropeptide Y (NPY), and somatostatin. Increased levels of DLX-2, GADs, and calretinin proteins were confirmed upon differentiation. L2.2 cells differentiated into neurons that fired action potentials in vitro, and their electrophysiological differentiation was accelerated and more complete when cocultured with developing astroglial cells but not with conditioned medium from these cells. The combined results suggest that clone L2.2 resembles GABAergic interneuron progenitors in the developing forebrain.
Li
Hedong
H
W. M. Keck Center for Collaborative Neuroscience, Rutgers, State University of New Jersey, Piscataway, New Jersey 08854-8082, USA. hedong@rci.rutgers.edu
Han
Yu R
YR
Bi
Caixia
C
Davila
Jonathan
J
Goff
Loyal A
LA
Thompson
Kevin
K
Swerdel
Mavis
M
Camarillo
Cynthia
C
Ricupero
Christopher L
CL
Hart
Ronald P
RP
Plummer
Mark R
MR
Grumet
Martin
M
D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002469:Cell Separation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology; D002999:Clone Cells; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D007395:Interneurons / Q000502:physiology*; D008280:Magnetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D014404:Tubulin / Q000378:metabolism
C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D017077:Culture Media, Conditioned; D009419:Nerve Tissue Proteins; D014404:Tubulin; D016222:Fibroblast Growth Factor 2