The Purkinje neuron acts as a central regulator of spatially and functionally distinct cerebellar precursors.
The prospective white matter (PWM) in the nascent cerebellum contains a transient germinal compartment that produces all postnatally born GABAergic inhibitory interneurons and astrocytes. However, little is known about the molecular identity and developmental potential of resident progenitors or key regulatory niche signals. Here, we show that neural stem-cell-like primary progenitors (Tnc(YFP-low) CD133(+)) generate intermediate astrocyte (Tnc(YFP-low) CD15(+)) precursors and GABAergic transient amplifying (Ptf1a(+)) cells. Interestingly, these lineally related but functionally divergent progenitors commonly respond to Sonic hedgehog (Shh), and blockade of reception in TNC(YFP-low) cells attenuates proliferation in the PWM, reducing both intermediate progenitor classes. Furthermore, we show that Shh produced from distant Purkinje neurons maintains the PWM niche independently of its classical role in regulating granule cell precursor proliferation. Our results indicate that Purkinje neurons maintain a bidirectional signaling axis, driving the production of spatially and functionally opposed inhibitory and excitatory interneurons important for motor learning and cognition.
Department of Cell and Developmental Biology, Vanderbilt University Medical Center, 4114 MRB III, Nashville, TN 37232, USA.
Jonathan T
JT
Fleming
Wenjuan
W
He
Chuanming
C
Hao
Tatiana
T
Ketova
Fong C
FC
Pan
Christopher C V
CC
Wright
Ying
Y
Litingtung
Chin
C
Chiang
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D051379:Mice; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D011689:Purkinje Cells / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D053823:Hedgehog Proteins; D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid