Transventricular delivery of Sonic hedgehog is essential to cerebellar ventricular zone development.
Cerebellar neurons are generated from two germinal neuroepithelia: the ventricular zone (VZ) and rhombic lip. Signaling mechanisms that maintain the proliferative capacity of VZ resident progenitors remain elusive. We reveal that Sonic hedgehog (Shh) signaling is active in the cerebellar VZ and essential to radial glial cell proliferation and expansion of GABAergic interneurons. We demonstrate that the cerebellum is not the source of Shh that signals to the early VZ, and suggest a transventricular path for Shh ligand delivery. In agreement, we detected the presence of Shh protein in the circulating embryonic cerebrospinal fluid. This study identifies Shh as an essential proliferative signal for the cerebellar ventricular germinal zone, underscoring the potential contribution of VZ progenitors in the pathogenesis of cerebellar diseases associated with deregulated Shh signaling, and reveals a transventricular source of Shh in regulating neural development.
Huang
Xi
X
Department of Cell and Developmental Biology, Center for Molecular Neuroscience, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Liu
Jiang
J
Ketova
Tatiana
T
Fleming
Jonathan T
JT
Grover
Vandana K
VK
Cooper
Michael K
MK
Litingtung
Ying
Y
Chiang
Chin
C
D000818:Animals; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D021381:Protein Transport; D015398:Signal Transduction; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D053823:Hedgehog Proteins; D008024:Ligands; C465570:Shh protein, mouse; D005680:gamma-Aminobutyric Acid
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