Lack of neurotrophin-3 results in death of spinal sensory neurons and premature differentiation of their precursors.
To understand mechanisms resulting in the absence of two-thirds of spinal sensory neurons in mice lacking NT-3, we have compared dorsal root ganglia development in normal and mutant embryos. The reduction in neurons, achieved by E13, results from several deficits: first, elevated neuronal apoptosis significantly reduces neuronal numbers; second, elevated neurogenesis between E11 and E12, without changes in rates of precursor proliferation or apoptosis, depletes the precursor pool; consequently, the reduced precursor pool prevents increases in neuronal numbers between E12 and E13, when most neurons are born in normal animals. Although deficits occur before final target innervation, we show that NT-3 is expressed at all stages in regions accessible to these neurons or their axons and is only restricted to final targets after innervation.
Fariñas
I
I
Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco 94143-0724, USA.
Yoshida
C K
CK
Backus
C
C
Reichardt
L F
LF
D000818:Animals; D016923:Cell Death; D002454:Cell Differentiation; D005314:Embryonic and Fetal Development; D005727:Ganglia, Spinal / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D051379:Mice / Q000196:embryology; D008817:Mice, Mutant Strains; D009414:Nerve Growth Factors / Q000172:deficiency*; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D020933:Neurotrophin 3; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors
D009414:Nerve Growth Factors; D020933:Neurotrophin 3