Original Paper
Folia Phoniatr Logop 2010;62:263270
DOI: 10.1159/000316962
Functional Histology of the Macula Flava in the
Human Vocal Fold Part 2: Its Role in the Growth
and Development of the Vocal Fold
Kiminori Sato Hirohito Umeno Tadashi Nakashima
Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, Kurume, Japan
Key Words
Macula flava Human vocal fold Larynx Extracellular
matrix Vocal fold stellate cell Growth and development
Abstract
Objective: This study aims to clarify the role of the maculae
flavae (MFe) during growth and development of the human
vocal fold mucosa (VFM). Methods: Our current results con-
cerning the MFe in the human newborn, infant, and child
VFM are summarized. Results: Newborns already had imma-
ture MFe at the same sites as adults. They were composed of
dense masses of vocal fold stellate cells (VFSCs), whereas ex-
tracellular matrix components were sparse. VFSCs in the
newborn MFe had already started synthesizing extracellular
matrices (EM). During infancy, the EM synthesized in the MFe
appeared in the VFM to initiate the formation of the three-
dimensional extracellular matrix structure of the human
VFM. During childhood, MFe including VFSCs continued to
synthesize EM such as collagenous, reticular, and elastic fi-
bers, and hyaluronic acid (glycosaminoglycan), which are es-
sential for the human VFM as a vibrating tissue. The MFe in
newborns, infants and children were related to the growth
and development of the human VFM. Conclusion: Human
MFe including VFSCs were inferred to be involved in the me-
tabolism of EM, essential for the viscoelasticity of the human
VFM, and are considered to be an important structure in the
growth and development of the human VFM.
Copyright 2010 S. Karger AG, Basel
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Published online: June 28, 2010
Introduction
In adults, the vocal fold (VF) has a layered structure
consisting of epithelium, lamina propria (superficial, in-
termediate and deep layer) and the vocalis muscle [1, 2].
The superficial layer is referred to as Reinkes space. The
structure consisting of the intermediate and deep layers
of the lamina propria is called the vocal ligament (fig. 1).
It runs between the anterior and posterior maculae flavae
(MFe, fig. 1). The mucosal portion of the layered struc-
ture is based on the differences of extracellular matrix
distribution; it is essential for VF vibration and phona-
tion [1].
The anterior MFe of the VF have already been de-
scribed as the nodulus elasticus in the anatomic textbook
by Lanz and Wachsmuth [3]. They said that the MFe were
elastic nodules located at the anterior end of the VF with
numerous elastic fibers [3]. Hirano [1] noted the MFe to
be masses of dense elastic fibers at the anterior and pos-
terior ends of the VF, referring to the former as the ante-
rior macula flava (nodulus elasticus) and the latter as the
posterior macula flava. The histological structure of the
MFe in the human vocal fold mucosa (VFM) is unique,
and their role in the VF as a vibrating tissue is interesting.
However, their role in the human VFM has not been clar-
ified until now [17].
During the past decade, we have investigated the mor-
phology of the MFe in the human VFM [822]. Human
adult MFe were found to be composed of dense masses of
Kiminori Sato, MD, PhD
Department of Otolaryngology-Head and Neck Surgery
Kurume University School of Medicine
67 Asahi-machi, Kurume 830-0011 (Japan)
Tel. +81 942 31 7575, Fax +81 942 37 1200, E-Mail kimisato @ oct-net.ne.jp
1 2
TC
ACT a TC
AMF
RS
VL
PMF
VP
Fig. 1. Human adult MFe and VFM. TC = Thyroid cartilage; ACT = anterior commissure tendon; AMF = an-
terior macula flava; PMF = posterior macula flava; VP = vocal process of arytenoid cartilage; RS = Reinkes
space; VL = vocal ligament.
Fig. 2. Human newborn (a), infant (b), and child (c) MFe and growth and development of the human VFM.
LP = Lamina propria of the VFM.
vocal fold stellate cells (VFSCs) and extracellular matri-
ces (EM) such as collagenous, reticular, and elastic fibers,
glycoprotein, and hyaluronic acid (glycosaminoglycan).
These EM are essential for the human VFM as a vibrating
tissue. The VFSCs in the human adult MFe form an in-
dependent cell category that should be considered a new
category of cells in the human VF.
On the basis of the results of our current study, human
MFe located at both ends of the VFM are inferred to be
involved in the metabolism of EM, essential for the vis-
coelastic properties of the lamina propria of the human
adult VFM [23]. Human adult MFe are inferred to be
responsible for maintaining the characteristic layered
structure of the human VFM [23]. Human adult MFe are
also considered to be an important structure in the aging
of the human VFM [23].
Human VF grows and develops, and its layered struc-
ture matures during adolescence [24, 25]. The purpose of
the present paper is to summarize the results of our cur-
rent morphological investigations into the MFe during
growth and development of the human VF.
Fine Structure of Newborn MFe and VFM (fig. 2a)
[1820]
The structures of the newborn VFM are immature
and differ from those of adults. In newborn VF, the entire
lamina propria appears as a uniform structure with no
vocal ligament, no Reinkes space or no layered structure
264 Folia Phoniatr Logop 2010;62:263270
b TC c TC
ACT ACT ACT
AMF AMF AMF
LP LP
LP
PMF PMF
PMF
VP VP
VP
[2, 1820]. The lamina propria of the newborn VFM is a
loose structure composed of ground substances and
sparse fibers. Ground substance is present and glycopro-
teins (fibronectin) are abundant in the lamina propria
[19]. The EM structure of the newborn VFM is incom-
plete.
Newborns have MFe at the same sites as adult VFM,
but they are immature. The MFe of the newborn VFM are
formed by dense masses of VFSCs (fig. 3, 4) and are situ-
ated bilaterally at the anterior and posterior ends of the
newborn VFM. They are round in shape and measure ap-
proximately 1 ! 1 ! 1 mm. In comparison with adult
MFe, the relative size is almost the same in both age
groups. The density of cells in the MFe is about 5 times
that in the adult MFe (fig. 5). On the other hand, fibro-
blasts are sparse in the lamina propria of the newborn
VFM. The density of fibroblasts in the newborn lamina
propria is about one eighth that of VFSCs in the newborn
MFe (fig. 5). The MFe are composed of VFSCs, elastic fi-
bers, reticular fibers, collagenous fibers, and ground sub-
stances. Cellular components are markedly abundant
and fibrous components are sparse. More collagenous fi-
bers are present than elastic fibers.
VFSCs in the newborn MFe are stellate or oval in shape,
and possess cytoplasmic processes (fig. 6a). The newborn
VFSCs are smaller in size than those of the adult, and
some cells form gap junctions with each other (fig. 6a). A
few lipid droplets are present in the cytoplasm but they are
Sato/Umeno/Nakashima
 a b

Fig. 3. Posterior macula flava (arrows) on

coronal section of the human newborn
VF. Cellular components are markedly
abundant and fibrous proteins are sparse.
TAM = Thyroarytenoid muscle. a Hema-
toxylin and eosin stain. b Elastica-van
Gieson stain. Original !40.

a b

Fig. 4. Light microscopy of the macula fla-

va of the human newborn VF. Arrows:
VFSCs. a Hematoxylin and eosin stain.
b Elastica-van Gieson stain. Original
!400.

much fewer than those found in adults. The lipid droplets
are 0.60.7 m in diameter, and are thus smaller than
those of adults. The nucleus-cytoplasm ratio is high, and
intracellular organelles, such as rough endoplasmic retic-
ulum and Golgi apparatus, are not very well developed.
Free ribosomes are well developed in the cytoplasm. Along
the periphery of the cytoplasm of the newborn VFSCs that
have developed intracellular organelles, a number of ves-
icles are present. Occasionally, a basal body (fetal rudi-
ments) is noted in the cytoplasm. These findings indicate
that the VFSCs in the newborn MFe are immature and
possess some features of mesenchymal cells. The morpho-
logical findings of the newborn VFSCs mentioned above
are recognized to various degrees.
In many types of tissue and cultured cells, the interiors
of adjacent cells communicate with each other through
cell-to-cell channels [26]. The fine structure of the cell-
to-cell channel has been well studied and defined as a gap
junction [26]. Cell communication is proposed to play an
important role in cell growth and differentiation [26].
The VFSCs in the newborn MFe may communicate with
each other for their growth and differentiation.

Role of Human Newborn, Infant, and Folia Phoniatr Logop 2010;62:263270 265
Child Vocal Fold Macula Flava
 300 p < 0.05 300

250 250

p < 0.05
200 200

Number/field
Number/field

p < 0.05
150 150

100 100
NS
NS
NS p < 0.05
50 50 NS

0 0
Newborn Infant Child Adult Aged Newborn Infant Child Adult Aged
a b

Fig. 5. Cell density in the human VFM [data from ref. 12, 21]. NS = Not significant. a VFSC density in the hu-
man macula flava. b Fibroblast density in the lamina propria.

a b

Fig. 6. Transmission electron microscopy of VFSCs in the human newborn macula flava (tannic acid stain).
a Synthesized collagenous and elastic fibers are detected around VFSCs. N = Nucleus; GJ = gap junction; CP =
cytoplasmic process; rER = rough endoplasmic reticulum; M = mitochondrion; CF = collagenous fibers; EF =
elastic fibers. b Synthesis of collagenous and elastic fibers by VFSCs. v = Vesicle; am = amorphous material;
mf = microfibril; cf = collagen fibril; el = elastin.

There are many collagenous fibers around the VFSCs
in the adult MFe in contrast with the newborn MFe
(fig. 4b). Few reticular fibers can be detected around the
newborn VFSCs. Electron microscopy indicates that the
newborn VFSCs have started to synthesize collagenous
and reticular fibers. Synthesis of collagenous and reticu-
lar fibers occurs in the same way as in the adult MFe.
There are some vesicles along the periphery of the cyto-
plasm, and newly released amorphous materials are pres-
ent on the cell surface of newborn VFSCs (fig. 6b). Micro-
fibrils 1015 nm in width are observed around the amor-
phous material. Collagen fibrils are detected near the
microfibrils (fig. 6b). Collagenous fibers are made up of
several collagen fibrils. Thus, the VFSCs have started to

266 Folia Phoniatr Logop 2010;62:263270 Sato/Umeno/Nakashima

synthesize not only collagenous fibers, but also reticular
fibers, in the human newborn MFe.
There are many elastic fibers around the VFSCs in
adult MFe, whereas not very many elastic fibers are pres-
ent around the VFSCs in the newborn MFe (fig. 4b). Elec-
tron microscopic study indicates that newborn VFSCs
start to synthesize elastic fibers. Synthesis of elastic fibers
is the same as in the adult MFe. There are some vesicles
at the periphery of the cytoplasm, and newly released
amorphous materials are seen on the cell surface of the
VFSCs. Microfibrils 1015 nm wide are situated around
the amorphous material. There are microfibril assem-
blies on which elastin is deposited (fig. 6b). The amor-
phous substance of the elastic fibers is produced by fusion
of microfibrils. The elastic fibers are composed of micro-
fibrils and amorphous substances. The former are abun-
dant, and the latter are sparse and reticular in shape, in-
dicating that the elastic fibers are immature. The number
of elastic fibers is small compared to that of collagenous
fibers in the newborn MFe.
The ground substance around the newborn VFSCs
is slightly stained light blue with Alcian blue at pH 2.5
and at pH 1. Glycosaminoglycan is situated around the
VFSCs, but not abundant, in the human newborn MFe.
The percentage of CD44-positive cells in the newborn
MFe is not very high, and 34.5 8 4.4% VFSCs are stained
with CD44 [12]. About 55% of the fibroblasts in the new-
born lamina propria are stained with CD44 [12]. In the
newborn VFM, before the appearance and distribution of
hyaluronic acid, CD44 is expressed in one third of the
VFSCs in the MF and one half of the fibroblasts in Rein-
kes space. This finding may be due to the fact that cells
and EM of the newborn VFM are immature.
To summarize, newborns have MFe at the same sites
of the VF as adults. Newborn MFe are formed by dense
masses of VFSCs, whereas extracellular matrix compo-
nents are sparse. The morphological characteristics of the
newborn MFe are not completely the same as those of
adults, but they are immature. The newborn VFSCs pos-
sess some features of mesenchymal cells. VFSCs in the
newborn MFe have already started synthesizing EM,
such as collagenous fibers, reticular fibers, elastic fibers,
and glycosaminoglycan, essential for the viscoelastic
properties of the human VFM, even though their struc-
ture is immature.
Fine Structure of Infant MFe and VFM (fig. 2b) [19]
In infancy, many reticular and collagenous fibers ex-
tend from the MFe toward the middle of the lamina pro-
pria, in which glycoprotein (fibronectin) is abundant,
Role of Human Newborn, Infant, and
Child Vocal Fold Macula Flava
and reticular and collagenous fibers increase throughout
the entire lamina propria of the infant VFM as compared
to that of newborns, and run roughly parallel to the VF
edge. Elastic fibers can be seen in the lamina propria of
the infant VFM at low density, and are composed of abun-
dant microfibrils and sparse and reticular amorphous
substances. The elastic fibers are immature, but increase
in amount over time in the lamina propria after collage-
nous and reticular fibers appear. No structure corre-
sponding to the vocal ligament can be found.
Fibronectin is a glycoprotein that serves as a template
for the oriented deposition of collagen [27]. It acts as an
interfibrillar stabilizing factor between collagen fibrils
and as a skeleton for elastic tissue formation and is in-
volved in the aggregation of proteoglycans [27]. Reticular
and collagenous fibers synthesized in infant MFe extend
towards the middle of the membranous portion of the
VF, in which fibronectin (glycoprotein) is abundant. Fi-
bronectin in the lamina propria appears to direct the ori-
ented deposition of reticular and collagenous fibers. Re-
ticular and collagenous fiber formation may be induced
in the lamina propria of infant VFM with growth. It de-
creases with the increase in fibrous components in the
lamina propria of the VFM. Fibronectin acts as an inter-
fibrillar stabilizing factor between collagen fibrils and is
involved in the aggregation of elastic fibers and glycos-
aminoglycan. Fibronectin acts as a skeleton for elastic tis-
sue formation in the human infant VFM.
The MFe of infant VFM are also dense masses of
VFSCs. The density of VFSCs in the infant MFe is
about 3 times that in the adult MFe and about two third
that in the newborn MFe (fig. 5). On the other hand, fi-
broblasts are sparse in the lamina propria of the infant
VFM. The density of fibroblasts is about one sixth that of
VFSCs in the infant MFe (fig. 5).
Infant MFe are composed of VFSCs, collagenous fi-
bers, reticular fibers, elastic fibers, and ground substanc-
es. Cellular components are more abundant than fibrous
components. However, fibrous components have in-
creased by comparison with those of the newborn MFe.
More reticular and collagenous fibers are present than
elastic fibers.
Many VFSCs in the infant MFe are stellate in shape,
possess cytoplasmic processes, and have a small nucleus-
cytoplasm ratio. The rough endoplasmic reticulum and
Golgi apparatus in the cytoplasm are developed. Newly
released amorphous material is present on the cell sur-
faces. Collagenous, reticular, and elastic fibers are seen
close to VFSCs.
Folia Phoniatr Logop 2010;62:263270 267
 The infant membranous portion of the VFM is stained
light blue with Alcian blue at pH 2.5; in particular, the
MFe are strongly stained. The material that stains with
Alcian blue (pH 2.5) is digested by hyaluronidase. Hyal-
uronic acid appears in the VFM and much hyaluronic
acid is produced around the VFSCs in the infant MFe.
Most of the VFSCs in the infant MFe are stained with
CD44. The percentage of CD44-positive cells in the in-
fant macula flava becomes larger, and 87.2 8 3.0% of the
stellate cells are stained with CD44 [12]. However, CD44-
positive fibroblasts become sparse (1.9 8 2.0%) in the
infant lamina propria of the VFM [12]. The expression of
CD44 and the distribution of hyaluronic acid are the
same as in the adult VFM. VFSCs and CD44 coopera-
tively start to play important roles in the maintenance of
hyaluronic acid in the human VFM during infancy.
To summarize, during infancy, EM synthesized in the
MFe appear in the lamina propria of the VFM between
the anterior and posterior MFe at different times to initi-
ate the formation of three-dimensional extracellular ma-
trix structure of the VFM that has the viscoelastic prop-
erties of a vibrating structure.
Fine Structure of Child MFe and VFM (fig. 2C) [21]
There are collagenous, reticular and elastic fibers in
the lamina propria of the child VFM. Vocal ligament and
layered structure are not present in the lamina propria of
the child VFM. The ground substance throughout the
VFM is stained light blue with Alcian blue at pH 2.5. The
material that stains in the lamina propria of the mucosa
with Alcian blue (pH 2.5) is digested by hyaluronidase.
Hyaluronic acid is present in the lamina propria of the
child VFM.
MFe are located bilaterally at the anterior and poste-
rior ends of the child VFM. They are approximately 1 !
1 ! 1 mm in size and consist of dense masses of VFSCs.
Many more VFSCs are distributed in the child MFe than
in those of adults. The density of VFSCs in child MFe is
about twice that in adult MFe, and about half that in new-
born MFe (fig. 5). On the other hand, fibroblasts are
sparse in the lamina propria of child VFM. The density
of fibroblasts is about one fourth that of VFSCs in child
MFe. The childs MFe are composed of VFSCs, collage-
nous fibers, reticular fibers, elastic fibers, and ground
substances. The fibrous components have increased by
comparison with those of the infant MFe.
The VFSCs are stellate and possess cytoplasmic pro-
cesses. A few lipid droplets are present in the cytoplasm,
but they are much fewer and smaller (0.61 m in diam-
eter) than those found in adults. Vitamin A is stored in
268 Folia Phoniatr Logop 2010;62:263270
their cytoplasm. The nucleus-cytoplasm ratio is relative-
ly small, and intracellular organelles, such as rough en-
doplasmic reticulum, are not very well developed. Free
ribosomes are present in the cytoplasm. Along the pe-
riphery of the cytoplasm of the childs VFSCs, vesicles are
present.
There are many collagenous, reticular, elastic fibers
around the VFSCs in the child MFe. Synthesis of these
fibers occurs in the same way as in adult MFe. The elec-
tron microscopic study indicates that the VFSCs in the
child MFe continue to constantly synthesize collagenous,
reticular, and elastic fibers.
Hyaluronic acid is present in the lamina propria,
in particular, in the MFe of the child VFM. Most of the
VFSCs (94.7 8 1.9%) in the child MFe are stained with
CD44 [12]. Almost all of the VFSCs in the child MFe
show CD44 expression and a large amount of hyaluronic
acid is present immediately adjacent to VFSCs in the
child MFe. On the other hand, CD44-positive fibroblasts
are sparse (5.6 8 3.0%) in the lamina propria of the child
VFM [12]. These findings are the same as those in adults.
The VFSCs in the MFe and CD44 both continue to play
roles in the metabolism of hyaluronic acid in the human
VFM during childhood.
To summarize, the child MFe are composed of dense
VFSCs and EM. The morphological characteristics of the
VFSCs in the child MFe are not completely the same as
those of adults. However, the VFSCs in the child MFe
have features characteristic of adult VFSCs and continue
to constantly synthesize EM, essential for viscoelastic
properties of the lamina propria of the human VFM as a
vibrating tissue. The child MFe including VFSCs con-
tinue to synthesize EM and EM have increased. MFe have
a role to play in the metabolism of EM of the VFM in the
stage of VF growth and development. The VFSCs in the
MFe are inferred to be involved in the growth and devel-
opment of human VFM.
Growth and Development of the Human VFM [22]
Among mammals, only humans can speak and only
human adult VF has a vocal ligament, Reinkes space, and
a layered structure [28]. Why do only human adults have
such a characteristic VF structure? Why and how does
newborn VFM grow, develop and mature? What are the
factors for initiating and continuing the growth of the
human VFM?
Tension is the most important factor which influences
the synthesis of collagenous fibers by fibroblasts [29, 30].
The bending stresses on the VF associated with phona-
tion are greatest in the region of the MFe [31]. We hypoth-
Sato/Umeno/Nakashima
esize that the tension caused by phonation (VF vibration)
after birth stimulates VFSCs in the anterior and poste-
rior MFe to accelerate production of EM and form the
vocal ligament, Reinkes space, and the layered structure
[18, 19].
Human adult VFM that remains unphonated (nonvi-
brated) after birth is hypoplastic and rudimentary, and
does not have a vocal ligament, Reinkes space or a layered
structure [22]. The MFe are atrophic and VFSCs have de-
creased activity [22]. These results support the hypothesis
that the tensions caused by phonation (VF vibration) af-
ter birth stimulate the VFSCs in the anterior and poste-
rior MFe to accelerate production of EM and form the
vocal ligament, Reinkes space and layered structure.
To summarize, VF vibration (phonation) after birth is
one of the important factors in the growth and develop-
ment of the human VFM. The tension caused by VF vi-
bration stimulates VFSCs in the MFe, and it is inferred
that the MFe are responsible for forming the characteris-
tic layered structure of the human VFM.
Conclusion
Newborns already have immature MFe which are
composed of dense masses of VFSCs at the same sites
as in the adult. Their cellular components are marked-
ly abundant and extracellular matrix components are
sparse. VFSCs in the newborn MFe have already started
the synthesis of EM.
During infancy, the EM synthesized in the MFe ap-
pear in the VFM to initiate the formation of three-di-
mensional EM structure of the human VFM.
In the child, MFe including VFSCs continue to syn-
thesize EM such as collagenous, reticular, and elastic fi-
bers, glycoprotein, and hyaluronic acid (glycosaminogly-
can), which are essential for the human VFM as a vibrat-
ing tissue. The MFe in newborns, infants and children
are connected with the growth and development of the
human VFM.
On the basis of the results of our current study, human
MFe located at both ends of the VFM are inferred to be
involved in the metabolism of EM, which is essential for
the viscoelastic properties of the lamina propria of the
human VFM. Human newborn, infant, and child MFe
are inferred to be responsible for forming the character-
istic layered structure of the human VFM. Human MFe
before adolescence are also considered to be an important
structure in the growth and development of the human
VFM.
Our current morphological results concerning the
MFe during growth and development of the human VFM
are summarized. More researches, especially using vari-
ous methods, are needed to validate the significance and
roles of the human MFe.

References
1 Hirano M: Phonosurgery: basic and clinical
investigations. Otologia (Fukuoka) 1975;
21(suppl 1):239260.
2 Hirano M, Sato K: Histological Color Atlas
of the Human Larynx. San Diego, Singular
Publishing Group, 1993.
3 Lanz TV, Wachsmuth W: Praktische Anato-
mie Hals. Berlin, Springer, 1955.
4 Subotic R, Vecerina S, Krajina Z, Hirano M,
Kurita S: Histological structure of vocal fold
lamina propria in foetal larynx. Acta Otolar-
yngol (Stockh) 1984;97:403406.
5 Vecerina-Volic S, Hirano M, Karovic-Krzelj
V: Macula flava in the vocal fold of human
fetus. Acta Otolaryngol (Stockh) 1988; 105:
144148.
6 Campos Banales ME, Perez Pinero B, Rivero
J, Ruiz Casal E, Lopez Aguado D: Histologi-
cal structure of the vocal fold in the human
larynx. Acta Otolaryngol (Stockh) 1995;115:
701704.
7 Fayoux P, Devisme L, Merrot O, Chevalier D,
Gosselin B: Histologic structure and devel-
opment of the laryngeal macula flava. Ann
Otol Rhinol Laryngol 2004; 113:498504.
8 Sato K, Hirano M: Histologic investigation
of the macula flava of the human vocal fold.
Ann Otol Rhinol Laryngol 1995; 104: 138
143.
9 Sato K, Hirano M, Nakashima T: Stellate
cells in the human vocal fold. Ann Otol Rhi-
nol Laryngol 2001; 110:319325.
10 Sato K, Hirano M, Nakashima T: Vitamin A-
storing stellate cells in the human vocal fold.
Acta Otolaryngol 2003;123:106110.
11 Sato K, Hirano M, Nakashima T: 3D struc-
ture of the macula flava in the human vocal
fold. Acta Otolaryngol 2003;123:269273.
12 Sato K, Sakamoto K, Nakashima T: Expres-
sion and distribution of CD44 and hyaluron-
ic acid in human vocal fold mucosa. Ann
Otol Rhinol Laryngol 2006; 115:741748.
13 Sato K, Shirouzu H, Nakashima T: Irradiated
macula flava in the human vocal fold mu-
cosa. Am J Otolaryngol 2008;29:312318.
14 Sato K, Miyajima Y, Izumaru S, Nakashima
T: Cultured stellate cells in human vocal fold
mucosa. J Laryngol Otol 2008; 122: 1339
1342.
15 Sato K, Hirano M, Nakashima T: Compara-
tive histology of the maculae flavae of the vo-
cal folds. Ann Otol Rhinol Laryngol 2000;
109:136140.
16 Sato K, Hirano M: Age-related changes of the
macula flava of the human vocal fold. Ann
Otol Rhinol Laryngol 1995; 104:839844.
17 Sato K, Hirano M, Nakashima T: Age-related
changes in vitamin A-storing stellate cells of
human vocal folds. Ann Otol Rhinol Laryn-
gol 2004;113:108112.
18 Sato K, Hirano M: Histologic investigation
of the macula flava of the human newborn
vocal fold. Ann Otol Rhinol Laryngol 1995;
104:556562.

Role of Human Newborn, Infant, and Folia Phoniatr Logop 2010;62:263270 269
Child Vocal Fold Macula Flava
19 Sato K, Hirano M, Nakashima T: Fine struc-
ture of the human newborn and infant vocal
fold mucosae. Ann Otol Rhinol Laryngol
2001;110:417424.
20 Sato K, Nakashima T: Vitamin A-storing
stellate cells in the human newborn vocal
fold. Ann Otol Rhinol Laryngol 2005; 114:
517524.
21 Sato K, Nakashima T: Stellate cells in the hu-
man child vocal fold macula flava. Laryngo-
scope 2009;119:203210.
22 Sato K, Nakashima T, Nonaka S, Harabuchi
Y: Histopathologic investigations of the un-
phonated human vocal fold mucosa. Acta
Otolaryngol 2008;128:694701.
270 Folia Phoniatr Logop 2010;62:263270
23 Sato K, Umeno H, Nakashima T: Functional
histology of the macula flava in the human
vocal fold. Part 1: Its role in the adult vocal
fold. Folia Phoniatr Logop, in press.
24 Hirano M, Kurita S, Nakashima T: Growth,
development and aging of human vocal
folds; in Bless DM, Abbs JH (eds): Vocal Fold
Physiology. San Diego, College-Hill Press,
1983, pp 2243.
25 Ishii K, Yamashita K, Akita M, Hirose H:
Age-related development of the arrangement
of connective tissue fibers in the lamina pro-
pria of the human vocal fold. Ann Otol Rhi-
nol Laryngol 2000; 109:10551064.
26 Kanno Y: Modulation of cell communication
and carcinogenesis. Jpn J Physiol 1985; 35:
693707.
27 Anderson JC: Glycoproteins of the connec-
tive tissue matrix; in Hall DH, Jackson DS
(eds): International Review of Connective
Tissue Research. New York, Academic Press,
1976, vol 7, pp 251322.
28 Kurita S, Nagata K, Hirano M: Comparative
histology of mammalian vocal folds; in
Kirchner JA (eds): Vocal Fold Histopatholo-
gy. San Diego, College Hill Press, 1986, pp
110.
29 Alberts B, Bray D, Lewis J, Raff M, Roberts
K, Watson JD: Molecular Biology of the Cell,
ed 3. New York, Garland Publishing, 1994.
30 Stopak D, Harris AK: Connective tissue
morphogenesis by fibroblast traction: tissue
culture observations. Dev Biol 1982;90:383
398.
31 Titze IR, Hunter EJ: Normal vibration fre-
quencies of the vocal ligament. J Acoust Soc
Am 2004;115:22642269.
Sato/Umeno/Nakashima
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