TGFbeta type II receptor signaling controls Schwann cell death and proliferation in developing nerves.
During development, Schwann cell numbers are precisely adjusted to match the number of axons. It is essentially unknown which growth factors or receptors carry out this important control in vivo. Here, we tested whether the type II transforming growth factor (TGF) beta receptor has a role in this process. We generated a conditional knock-out mouse in which the type II TGFbeta receptor is specifically ablated only in Schwann cells. Inactivation of the receptor, evident at least from embryonic day 18, resulted in suppressed Schwann cell death in normally developing and injured nerves. Notably, the mutants also showed a strong reduction in Schwann cell proliferation. Consequently, Schwann cell numbers in wild-type and mutant nerves remained similar. Lack of TGFbeta signaling did not appear to affect other processes in which TGFbeta had been implicated previously, including myelination and response of adult nerves to injury. This is the first in vivo evidence for a growth factor receptor involved in promoting Schwann cell division during development and the first genetic evidence for a receptor that controls normal developmental Schwann cell death.
D'Antonio
Maurizio
M
Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, United Kingdom.
Droggiti
Anna
A
Feltri
M Laura
ML
Roes
Jürgen
J
Wrabetz
Lawrence
L
Mirsky
Rhona
R
Jessen
Kristján R
KR
D000818:Animals; D000831:Animals, Newborn; D019771:Axotomy; D016923:Cell Death / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D004357:Drug Synergism; D004622:Embryo, Mammalian; D047108:Embryonic Development; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000502:physiology; D009409:Nerve Crush; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020890:Neuregulin-1 / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000172:deficiency / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism / Q000502:physiology*; D012584:Sciatic Nerve / Q000196:embryology* / Q000254:growth & development* / Q000293:injuries / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II