Experimental Dermatology 2003: 12: 233–236 Copyright # Blackwell Munksgaard 2003

Blackwell Munksgaard . Printed in Denmark

EXPERIMENTAL DERMATOLOGY
ISSN 0906-6705

Review Article

Mammalian skin evolution: a reevaluation

Maderson PFA. Mammalian skin evolution: a reevaluation. P. F. A. Maderson
Exp Dermatol 2003: 12: 233–236. # Blackwell Munksgaard, 2003 Department of Biology, Brooklyn College of City
University of New York, Brooklyn, NY, USA
Abstract: A 1972 model for the evolutionary origin of hair suggested a
primary mechanoreceptor role improving behavioral thermoregulation
contributed to the success of late Paleozoic mammal-like reptiles. An
insulatory role appeared secondarily subsequent to protohair
multiplication. That model is updated in light of new data on (a)
palaeoecology of mammalian ancestors; (b) involvement of HRPs in Key words: evolution – scales – hair –
keratinization; (c) lipogenic lamellar bodies that form the barrier to epidermis – HRPs – endothermy – barrier
cutaneous water loss; and (d) growth factors involved in hair follicle tissues
embryogenesis and turnover. It is now proposed that multiplication of Dr P. Maderson, Department of Biology, Brooklyn
sensory protohairs caused by mutations in patterning genes initially College of City University of New York, Brooklyn,
protected the delicate barrier tissues and eventually produced the minimal NY 11210, USA
morphology necessary for an insulatory pelage. The latter permitted Tel.: þ1 718 951 5706
Mesozoic mammals to occupy the nocturnal niche ‘in the shadow of Fax: þ1 718 951 4659
dinosaurs’. When the giant reptiles became extinct, mammals underwent e-mail: Maderson@brooklyn.cuny.edu
rapid radiation and reemerged as the dominant terrestrial vertebrates. Accepted for publication 16 August 2002

Introduction
Throughout the past 210 Myr, a time-traveler
interested in mammalian or avian skin would see
few differences from modern species. During the
142 Myr of the mid-late Mesozoic era (Fig. 1) (1),
early mammals scurried around at night ‘in the
shadow of dinosaurs’ (2). By day, giant reptiles
ruled the warm continents and oceans while early
birds flew above. The functional properties of fully
evolved pelages and plumages, respectively,
enabled mammals and birds to ‘bide their time’
waiting the demise of dinosaurs due to meteor
impact at the end of the Cretaceous 65 Myr ago.
Rocks of the 122 Myr preceding the Jurassic
document the early history of amniote vertebrates
(reptiles, mammals and birds), wherein we seek
clues to skin evolution.
Two features distinguish amniotes from amphib-
ians (frogs, salamanders, etc.) and fish: their
reproduction does not require water and they sur-
vive the dehydrating effects of life on land (1).
Mammals and birds independently evolved
endothermy (a physiologically regulated, constant,
body temperature) from their ectothermic (collo-
quially ‘cold-blooded’) reptilian ancestors (1).
Reconstructing the evolution of physiological
features involves evaluating fossils in light of data
concerning soft tissue form and function in living
species. Insulatory hairs and feathers are import-
ant to endothermy but how did they evolve?
Because the fossil record for proto-mammals is
chronologically more extensive and more detailed
than for proto-birds (2,3), it might seem easier to
trace the evolution of hair than of feathers. For
several technical reasons this is not so. Here, two
problems concern us. First, although the movie
‘Jurassic Park’ made dinosaurs (and their crocodil-
ian and avian cousins) familiar to non-specialists,
few know anything of mammalian forebears
(synapsid reptiles) (2,3) who emerged from Palaeo-
zoic coal swamps 300þ Myr ago, ruled the earth
for 120 Myr and became extinct when their
descendents were temporarily ‘side-lined’ by the
dinosaurs. Second, although we are certain that
hair evolved minimally 200 Myr BP, we lack any
direct evidence.
Lacking fossil evidence, surviving proto-mammals,
or any intermediates between hair and any known
epidermal derivative, how do we address the prob-
lem of mammalian skin origins? While ubiquity
of the insulatory role in extant taxa seems to
imply an early relation to the origin of endothermy,

233
Maderson

BEGAN
(Lasted) ORIGIN, DOMINANCE AND DEMISE OF
ERA PERIOD
Myr BP MAJOR VERTEBRATE GROUPS
(Myr)
Cenozoic

Surviving theropsid amniotes: - Modern Mammals

66
Tertiary Surviving sauropsid amniotes: - Birds, Turtles, Lizards,
(66)
Snakes and Crocodiles
Mass extinctions of reptiles probably caused by meteor impact
144 Late Mesozoic Mammals
Cretaceous
(78) Ruling Reptiles (Sauropsids)*; Birds
Mesozoic

Early Mammals*
208 Figure 1. Vertebrate history in a
Jurassic Ruling Reptiles (Sauropsids)*
(64) geological context. Asterisks mark
Archaeopteryx – 1st feathered bird*
groups known only as fossils. Lineages
Late radiation and decline of mammal-like reptiles*, and taxa mentioned in the text shown
245
Triassic among whom were the ancestors* of all later Mammals in various fonts. After 200 Myr of
(37)
Origin Ruling and Modern Reptiles aquatic life, the first Tetrapods (four
286
Sail reptiles* Mammal-like reptiles (Synapsids)*
limbed) evolved from fish ancestors.
Permian
(41) These Amphibians radiated in the Coal
Anthracosaurs* Basal amniotes*, swamps of the Mississippian and
Late Paleozoic

330 that were the ancestors of:- Pennsylvanian periods giving rise to
Pennsylvanian
(44) (a) “theropsid lineage” (Synapsids + Mammals) and (!) the ancestors of modern amphibians
(b) “sauropsid lineage” (other reptiles + birds) (frogs, toads and salamanders) and the
360 Anthracosaurs – amniote ancestors.
Mississippian Radiation Amphibia ? origins modern forms
(30) Basal amniotes soon ! organisms
408 included generically in either the
Devonian Fish Primitive Tetrapods (Amphibia) Theropsid lineage comprising Synapsid
(48)
reptiles and mammals or the Sauropsid
Paleozoic

Silurian
Early

590 lineage comprising turtles and all living

Mid

Ordovician Origin and radiation of jawless and early jawed fish

(total 182) reptiles, the denizens of Jurassic Park,
Cambrian
and birds. Data from (1).

basic physics show that initial changes in a
reptilian integument could not have been directly
related to such (4). Can we identify a plausible pri-
mary role for changes in a scaled skin that could
lead eventually to ‘hair-like structures’?
A model for the origin of mammalian hair
On the assumption that the success of synapsid
reptiles aeons before the ‘Age of Dinosaurs’
reflected some metabolic advantage, Maderson
(5) offered a model proposing that: ‘. . . hairs
arose from highly specialized sensory appendages
of mechanoreceptor function which facilitated
thermoregulatory behavior in early synapsids.
. . .[A later chance mutation multiplied morpho-
genetic fields responsible for original, sparsely
arranged ‘protohairs’ and produced a ‘proto-
pelage’ whose properties were the subject of subse-
quent selection in an insulatory context although
sensory function remained important]’.
Because of absence of relevant data this model
ignored, or addressed inadequately, several ques-
tions: 1) In what environments did amniote skin
evolution occur? 2) When and how did amniotes
acquire a barrier to cutaneous water loss (CWL)?
3) Why did early synapsids reduce and lose their
scales? 4) How did multiplication of hypothesized
protohairs occur and what initial selective advan-
tages accrued therefrom? These shortcomings have
been ameliorated by data and interpretations from
several different research programs and a new
appreciation of complexity of form-function inter-
play in skin: we now see that scales in reptiles and
epidermal appendages in mammals and birds
(hairs and feathers) have important roles of
mechanical protection at both organismic and
tissue levels (6).
New data ameliorate deficiencies of the original
model and reveal the unaddressed questions to be
inter-related
Palaeontologists who reconstruct the ecology of
extinct species suggest that while amniotes ori-
ginated on islands in coal swamps 300 Myr BP,
perhaps in pursuit of insects for food, ‘truly terres-
trial’ ecosystems wherein synapsids faced poten-
tially desiccating and mechanically abrasive
environmental factors may not have emerged
until 250 Myr BP (7).
Two conclusions relevant to mammalian skin
origins emerge from studies of skin structure and
development in reptiles and birds (4,8,9). The clas-
sic notion of ‘hard’ and ‘soft’ keratins/keratinized
tissues has been ‘refined’ by the realization that
corneous tissues may be based on either a- or
b-proteins. A primordial histidine-rich protein

234

(HRP) originated as a feature of amniote
a-keratogenesis later expressed as keratohyalin
granules (KHGs) in mammals and keratohyalin-
like granules (KHLGs) in reptiles and birds.
Another amniote epidermal feature is the asso-
ciation of lipogenic lamellar bodies (LBs) with
a-keratogenic tissues reducing CWL (10). However,
different barrier cytologies in at least three lineages
imply independent acquisition (4,10), so that
perhaps parental coping with CWL constrained
emergence of ‘full terrestrialism’ – not reproductive
mode (1)!
A plausible explanation for scale reduction and
loss in early synapsids is that Theropsid amniotes
[‘Sail’ and ‘Mammal-like’ reptiles plus mammals
(Fig. 1)] pursued a different strategy to cope with
environmental abrasion of their skin than that
seen in other reptiles (Sauropsids) although, inter-
estingly, birds ‘copied’ this strategy when feathers
evolved (4,6). The nature of, and basis for, the
hypothesized theropsid strategy can be summar-
ized. A mutation involving a molecular trigger
involved in patterning produced the initial multi-
plication of mechanosensory ‘protohairs’ and the
resultant ‘protopelage’ had an initial selective
advantage in that it was the final step in providing
a tissue to protect the barrier to CWL. Later, as
endothermy was gradually perfected in early mam-
mals, perhaps a Jurassic event when they occupied
the nocturnal niche (11), an insulatory boundary
was further improved by multiplication of non-
tactile hairs.
New molecules, organelles and tissues in the
evolution of form and function in vertebrate
skin – a synthesis
Introduction
Mammalian skin evolution is best understood
against a background of two basic facts. First,
vertebrate skin is geometrically patterned whether
comprising scales or appendages (5). Second,
several ‘new’ molecules, organelles and therefore
cytodifferentiative events producing tissue
differences have characterized epidermal history
(Fig. 2) (4).
Events in early tetrapods
Throughout evolution the overall mucogenicity of
vertebrate epidermis has been steadily reduced and
in amniotes it is expressed only in oral, genital and
anal mucus membranes.
In amphibians, enhancement of a-keratogeni-
city (primitively represented in all fish by 70A
tonofilaments) by a ‘cell envelope’ (marginal
Evolution of mammalian skin
layer containing involucrin) permitted formation
of a stratified, cornified epidermis (12,13). It is no
barrier to CWL so that most species are confined
to ‘wet and therefore mechanically lubricating’
environments (1).
In Palaeozoic, anthracosaurian amphibians, or
‘Basal Amniotes’ (Figs 1 and 2), a- keratinization
was enhanced by filaggrin derived from a primor-
dial Histidine Rich Protein (pHRP) (14). Lipo-
genic lamellar bodies (LBs) might have provided
some barrier to CWL, but the ‘delicate’ epidermal
tissues covering scales were susceptible to abrasion
so that organisms were still restricted to a ‘wet’
aquatic environment (4).
Two different strategies in amniotes
In Sauropsid Amniotes, mechanical protection
derives from the b-keratogenic epidermal tissues
covering reptilian scales, or avian feathers (4,6).
Sauropsid HRP, represented by KHLGs, is
involved in vertical alternation between a- and b-
keratogenesis (4,9). The barrier to CWL is housed
in a-keratogenic tissues that are protected by over-
lying b-keratogenic tissues. Their various degrees
of efficacy permitted exploitation of desiccating
and abrasive terrestrial niches.
Early Theropsid Amniotes evolved a skin struc-
turally and functionally similar to that of modern
toads, living amphibians whose reduced epidermal
mucogenicity and cornification (4) permits them to
walk over dusty driveways and hide in garages!
Theropsids lost scales because their a-keratogenic
epidermis was somewhat toughened by mamma-
lian-type HRP (KH), and the derived hydrophilic
filaggrin facilitates epidermal flexibility (14). Their
barrier tissues, whose minimal efficacy is suggested
by the environments they inhabited, remained
susceptible to abrasion unless ‘lubricated’ regu-
larly. These organisms almost certainly practiced
‘behavioral thermoregulation’ as do many
living frogs and toads, and this behavior was
facilitated by the spatially patterned sensory pro-
tohairs (5).
In late Theropsid Amniotes, multiplication of
protohairs, caused perhaps by a mutation leading
to up-regulation of a patterning trigger such as
b-catenin (15), provided the necessary enhanced
mechanical protection for the thin stratum
corneum. Once the included barrier tissues were
less susceptible to abrasion, exploration of ‘true
terrestrial’ niches became possible.
In basal Mammals, the ‘protopelage’ – whose
constituent units might have been strengthened by
trichohyalin (14), to form ‘true hairs’ – had dual
roles. First, an increased density of hairs further
235
Maderson
1
2 3
Tetrapods
4?
Amniotes
4?
5 Mammal-like
Theropsids
6 reptiles*
7
8 Basal
Sauropsids
9 1996.
Figure 2. Evolutionary history of some molecules, organelles and
tissues that characterize the skin of tetrapod vertebrates. Arrows
on branching cladogram show origins of major lineages,
emphasizing Theropsid Amniotes (Mammals and their reptilian
antecedents). Groups mentioned in text are shown in the same
font as in Figure 1. Asterisks indicate those known only as fossils.
‘Dinosaurs’*# include bird ancestors. Major skin changes
indicated by numbered boxes. [1] Epidermal covering of
patterned scales comprises mucogenic cells containing 70A
tonofilaments indicating a-keratogenic potential. [2] Primitively,
tetrapods bore scales covered by a stratified, squamous epidermis
whose cells possessed an envelope and showed reduced
mucogenesis compared with ancestral fish. [3] Modern
amphibians have lost patterned scales. [4?] In some Paleozoic
amphibia or perhaps basal amniotes (4), major changes in
epidermal structure facilitated a more terrestrial life-style: further
reduction in mucogenicity accompanied a-keratogenesis
enhanced by filaggrin derived from a primordial Histidine Rich
Protein (pHRP) and keratinocytes formed lipogenic lamellar
bodies. [5] Theropsid amniotes soon reduced and lost patterned
scales and epidermal a-keratogenesis involved keratohyalin
granules. [6] Spatially patterned epidermal appendages –
‘mechanosensory protohairs’ – facilitated behavioral
thermoregulation (5). [7] Multiplication of protohairs caused by
changes in patterning molecules initially protected delicate
barrier tissues and formed a ‘protopelage’ whose insulatory
properties permitted refinement of mammalian endothermy. [8]
In reptilian sauropsids, b-keratogenic epidermal tissues covering
scales protect the subjacent a-keratogenic tissues that house the
barrier to CWL. Vertical alternation between a- and
b-keratogenesis involves keratohyalin-like granules (4). [9] In
birds, replacement of scales by epidermal appendages – feathers –
protects barrier tissues and facilitates both flight and avian
endothermy.
improved mechanical protection of inter-follicular
barrier tissues (4,6). Second, this density also
permitted an insulatory function that could have
been further enhanced by other changes in the
patterning mechanisms (17).
Concluding comments
Hypothetical models of this type do not solve
evolutionary questions and are not intended to
236
Bony fish
do so. Their value lies in the fact that continual
incorporation of new data from a variety of bio-
Modern amphibia
logic disciplines into such models, and/or present-
Anthracosaurs* ation of new models to supplant them enhances
Basal amniotes*
the probability that new research programs
Sail reptiles*
addressing empirically refutable hypotheses will
emerge from such interdisciplinary considerations.
Mammals
References
sauropsids*
Living reptiles
1. Pough F H, Heiser J B, McFarland W N. Vertebrate
Life, 4th edn. Upper Saddle River, NJ: Prentice Hall,
“Dinosaurs”*#
Birds
2. Currie P J, Padian K, eds. Encyclopedia of Dinosaurs.
San Diego, CA: Academic Press, 1997.
3. Carroll R L. Vertebrate Paleontology and Evolution.
New York, NY: Freeman, 1988.
4. Maderson P F A, Alibardi L. The development of the
sauropsid integument: a contribution to the problem
of the origin and evolution of feathers. Am Zool 2000:
40: 513–529.
5. Maderson P F A. When? Why? and How? Some specu-
lations on the evolution of the vertebrate integument.
Am Zool 1972: 12: 159–171.
6. Maderson P F A, Rabinowitz B, Tandler B, Alibardi L.
Ultrastructural contributions to an understanding
of the cellular mechanisms involved in lizard skin
shedding with comments on the function and evolution
of a unique lepidosaurian phenomenon. J Morph 1998:
236: 1–24.
7. Gordon M S, Olsen E C. Invasions of the Land. New
York, NY: Columbia University Press, 1995.
8. Sawyer Rh, Glenn T, French J O et al. The expression
of beta (b) keratins in the epidermal appendages of
reptiles and birds. Am Zool 2000: 40: 530–539.
9. Alibardi L. Keratohyalin-like granules in lizard epider-
mis: evidence from cytochemical, autoradiographic and
microanalytical studies. J Morph 2001: 284: 64–79.
10. Menon G K, Menon J. Avian epidermal lipids: func-
tional considerations and relationship to feathering.
Am Zool 2000: 40: 540–552.
11. Ruben J A, Jones T D. Selective factors associated
with the origin of fur and feathers. Am Zool 2000:
40: 585–596.
12. Polakowska R R, Goldsmith L A. The cell envelope
and transglutaminases. In: Goldsmith L A, ed. Physi-
ology, Biochemistry and Molecular Biology of the
Skin, 2nd edn. 2 vol. Oxford: Oxford University
Press, 1991: 168–170.
13. Matolsy A G. Concluding remarks and future direc-
tions. Curr Topics Dev Biol 1987: 22: 255–264.
14. Resing K A, Dale B A. Proteins of keratohyalin. In:
Goldsmith L A, ed. Physiology, Biochemistry and
Molecular Biology of the Skin, 2nd edn. 2 vol. Oxford:
Oxford University Press, 1991: 148–167.
15. Gat U, DasGupta L, Degenstein L, Fuchs E. De novo
morphogenesis and hair tumors in mice expressing a
truncated beta-catenin in skin. Cell 1998: 95: 606–614.
16. Stenn K S, Paus R. Controls of hair follicle cycling.
Physiol Rev 2001: 81: 449–494.
17. Chuong C M, ed. Molecular Basis of Epithelial Append-
age Morphogenesis. Austin, TX: R. G. Landes, 1998.