Trks and p75 genes are differentially expressed in the inner ear of human embryos. What may Trks and p75 null mutant mice suggest on human development?
Ja. Vega et al., Trks and p75 genes are differentially expressed in the inner ear of human embryos. What may Trks and p75 null mutant mice suggest on human development?, NEUROSCI L, 272(2), 1999, pp. 103-106
Recent work has shown the expression of Neurotrophins low (p75) and high af
finity (Trk's A, B, and C) receptors in the developing inner ear sensory ne
urons of chick and mouse. Likewise the biological significance of such rece
ptor expression was demonstrated by using both Trks and Neurotrophins null
mutant mice. The present study was conducted to determine the expression of
Trks and p75 proteins in the human inner ear throughout development. Hence
to assess the potential role of Neurotrophins in the development of audito
ry and vestibular specific innervation in man. In other words, we intend to
address the issue whether or not what null mutant mice for Trks and p75 ha
ve revealed on inner ear development may be relevant for human embryos. Fif
ty-two inner ears and their cochleovestibular ganglions (CVG) from human em
bryos and fetuses, ranging from 5 to 24 weeks of pregnancy were analyzed. B
oth Western blot and immunocytochemistry on frozen sections were used as co
mplementary procedures. Quantitative Western blot studies revealed that Trk
-B and C immunoreactivity (IR) appeared by embryonic week 5 in CVG neurons,
increased at high levels between embryonic weeks 7 and 12, and later on, i
n 15 week-old specimens and older began to decrease to minimal levels. Trk-
A IR was detected at just moderate levels during 5 and 7 weeks reflecting t
he presence of NGF high affinity receptors only at these earlier developmen
tal ages. The p75 IR was detected at high degrees in the early stage of the
5th week and at abundant levels in all studied inner ears from the 7th to
the 24th pregnancy week. These Western blot observations were corroborated
by immunocytochemistry on frozen sections, which also revealed a major dist
ribution of both p75 and Trks on neuronal bodies while p75 appears localize
d on supporting cells. Our findings reveal a tight correlation between p75
and Trks expression throughout human development and specific inner ear dev
elopmental events, such as target-dependent neuronal cell death and afferen
t hair cells innervation. That kind of association of p75 and Trks temporal
pattern with distinctive steps in inner ear developmental schedule, is a f
eature shared between human embryos and other mammals, such as mouse. Based
on the present results and considering them together with the reported phe
notype of p75 and Trks null mutant mice, we hypothesize that p75 and Trk re
ceptors, as well as, their binding Neurotrophins may be essential in human
inner ear development. Accordingly, they may be required molecules for sens
ory epitheliums innervation and target-dependent neuronal cell death, durin
g embryogenesis and even early postnatal life, in man. (C) 1999 Elsevier Sc
ience Ireland Ltd. All rights reserved.