Developing Schwann cells acquire the ability to survive without axons by establishing an autocrine circuit involving insulin-like growth factor, neurotrophin-3, and platelet-derived growth factor-BB.
Although Schwann cell precursors from early embryonic nerves die in the absence of axonal signals, Schwann cells in older nerves can survive in the absence of axons in the distal stump of transected nerves. This is crucially important, because successful axonal regrowth in a damaged nerve depends on interactions with living Schwann cells in the denervated distal stump. Here we show that Schwann cells acquire the ability to survive without axons by establishing an autocrine survival loop. This mechanism is absent in precursors. We show that insulin-like growth factor, neurotrophin-3, and platelet-derived growth factor-BB are important components of this autocrine survival signal. The secretion of these factors by Schwann cells has significant implications for cellular communication in developing nerves, in view of their known ability to regulate survival and differentiation of other cells including neurons.
Meier
C
C
Department of Anatomy and Developmental Biology, University College London, London, WC1E 6BT, United Kingdom.
Parmantier
E
E
Brennan
A
A
Mirsky
R
R
Jessen
K R
KR
D000818:Animals; D000937:Antigen-Antibody Reactions; D019898:Autocrine Communication / Q000502:physiology; D001369:Axons / Q000502:physiology*; D000077214:Becaplermin; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D017077:Culture Media, Conditioned; D006023:Glycoproteins / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000502:physiology*; D020880:Neuregulins; D020933:Neurotrophin 3; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000502:physiology* / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism; D013002:Somatomedins / Q000502:physiology*
D017077:Culture Media, Conditioned; D006023:Glycoproteins; D009414:Nerve Growth Factors; D020880:Neuregulins; D020933:Neurotrophin 3; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D013002:Somatomedins; D000077214:Becaplermin; D017871:Calcium-Calmodulin-Dependent Protein Kinases