Prenatal and postnatal requirements of NT-3 for sympathetic neuroblast survival and innervation of specific targets.
Postnatal homozygous neurotrophin-3 mutant mice display a loss of about half the sympathetic superior cervical ganglion (SCG) neurons (Ernfors, P., Lee, K.-F., Kucera, J. and Jaenisch, R. (1994a) Cell 77, 503-512; Farinas, I., Jones, K. R., Backus, C., Wang, X. Y. and Reichardt, L. F. (1994) Nature 369, 658-661). We found that this loss is caused by excessive apoptosis of sympathetic neuroblasts leading to a failure to generate a normal number of neurons during neurogenesis. NT-3 was also found to be required postnatally. In Nt-3-/- mice, sympathetic fibers failed to invade pineal gland and external ear postnatally; whereas other targets of the external and internal carotid nerves, including the submandibular gland and the iris, displayed a normal complement of sympathetic innervation. Sympathetic fibers of mice carrying one functional copy of the Nt-3 gene (Nt-3+/- mice) invaded the pineal gland, but failed to branch and form a ground plexus. Cultured neonatal sympathetic neurons responded to NT-3 by neurite outgrowth and mRNA upregulation of the NT-3 receptor, trkC. Exogenously administered NT-3 promoted sympathetic growth and rescued the sympathetic target deficit of the mutant mice. We conclude that NT-3 is required for the survival of sympathetic neuroblasts during neurogenesis and for sympathetic innervation and branching in specific targets after birth.
ElShamy
W M
WM
Department of Medical Biochemistry and Biophysics, Laboratory of Molecular Neurobiology, Karolinska Institute, Stockholm, Sweden.
Linnarsson
S
S
Lee
K F
KF
Jaenisch
R
R
Ernfors
P
P
D000375:Aging / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D002478:Cells, Cultured; D005314:Embryonic and Fetal Development; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005865:Gestational Age; D006720:Homozygote; D007150:Immunohistochemistry; D051379:Mice; D008818:Mice, Neurologic Mutants; D008938:Mitosis; D009412:Nerve Fibers / Q000502:physiology; D009414:Nerve Growth Factors / Q000172:deficiency / Q000235:genetics* / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D020933:Neurotrophin 3; D010870:Pineal Gland / Q000196:embryology / Q000254:growth & development; D011247:Pregnancy; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D017475:Receptors, Nerve Growth Factor; D014446:Tyrosine 3-Monooxygenase; D020794:Receptor Protein-Tyrosine Kinases; D020812:Receptor, trkC