Cellular proliferation during cicatrization of the skin of 7-day chick embryos cultured in vitro

A cell proliferation study during in vitro wound healing of dorsal thoraco-lumbar skin of 7-day chick embryos was performed by pulse labelling using a single isotope (tritiated thymidine). The unoperated (controls) and operated explants were incubated in the radioactive medium (1 microCi/ml tritiated thymidine) 1 h prior to fixation and where fixed 1 h (start control), 48, 72 and 96 h after the excision. Mean labelling and mitotic indices of the unwounded epidermis were, respectively, 18.22% and 2.66% at 7 days, and 7.03% and 0.88% at 11 days (7 days + 96 h). 72 h after the excision, the labelling and mitotic indices of wounded epidermis increased, on average, respectively to 212,5% and 220% with respect to those of the controls, in the proximal zones near the inner edge on the wound. The labelling and mitotic indices in the dermis were, respectively, 27.95% and 3.63% at 7 days and 7.65% and 1.30% at 11 days. 72 h after the excision, the labelling and mitotic indices of the operated dermis increased, on average, respectively to 220% and 130% with respect to those of the controls in the centre and the proximal zones of the wound. The increase of the labelling index of the operated integument persisted for a maximum of 24 h, between 48 to 72 hours after the excision.     

Cicatrization of the skin of the 7-day-old chick embryo cultured in vitro

A morphological study of in vitro wound healing has been performed by light, transmission and scanning electron microscopy in dorsal thoraco-lumbar skin of 7-day chick embryos. A circular wound, 750 microns in diameter, was punched out of dorsal skin, removing epidermis and the underlying dense dermis. Wound closure was completed within 96 to 120 hours. Feather bud development was not observed at the wound site. The epidermis began to migrate some 24 h after the wounding; the migration of peridermal cells preceded that of basal epidermal cells by some 12 hours. Mechanisms of the epidermal migration were similar to those observed in situ during wound healing of the integument in 5-day chick embryos (THEVENET, 1981), Superficial epithelization of bare dermis occurred as soon as 12 h after the injury. Cytoplasm of dermal cells exhibited many microtubules and a dilated rough endoplasmic reticulum. During the first 48 h, the epidermal cells established direct contacts and zones of close parallel apposition with epithelized dermal cell processes. The basement membrane lamina densa was maintained at the edges of the wound without retraction or ruffling. It was reconstituted concomitantly with the epidermal migration within 72 h. Cytoplasm of migratory epidermal and epithelized dermal cells exhibited many cytoskeleton structures.     

Naturally occurring wounds and wound healing in chick embryo wings

Summary Spontaneous cutaneous wounds occur in avian embryos (chick, duck, quail) in various prominent parts of the body, notably the elbow, the knee and the outer face of feather buds. The frequency and size and the light and electron microscopic morphology of elbow wounds in the chick embryo are described. The cutaneous lesion appears in over 80% of the embryos at around 7 days of incubation, persists through 14 days, and finally heals completely at around 16 days of incubation. No trace of the wound is visible after that age. Wound healing of these spontaneous lesions was analysed with light microscopy (using indirect immunofluorescence for the localization of type I collagen, fibronectin and laminin) and electron microscopy. The main feature of the very slow healing process, as compared with the rapid cicatrization of experimental excision wounds, appears to be a continuous damage of the healing epidermis, until, finally, definitive wound closure occurs between 14 and 16 days of incubation. In the damaged region, where the epidermis is absent, the dermis exhibits an increased density of type I collagen fibres and of fibronectin. The upper face of the bare dermis is deprived of laminin. Spontaneous lesions do not occur in isolated wings explanted on the chick chorioallantoic membrane, where the wings do not become mobile and are not in contact with the amnion. The observations and explantation experiments suggest that the skin damage is caused by friction and abrasion of the bending elbow against the amnion or the amniotic fluid.     

Temporal distribution of 5BrdU-labelled cells suggests that most injured tissues contribute proliferating cells for the regeneration of the tail and limb in lizard

After tail and limb amputation in lizard, injection of 5BrdU for 6 days produces immunolabelled cells in most tissues of tail and limb stumps. After further 8 and 16 days, and 14 and 22 days of regeneration, numerous 5BrdU-labelled cells are detected in regenerating tail and limb, derived from most stump tissues. In tail blastema cone at 14 days, sparse-labelled cells remain in proximal dermis, muscles, cartilaginous tube and external layers of wound epidermis but are numerous in the blastema. In apical regions at 22 days of regeneration, labelled mesenchymal cells are sparse, while the apical wound epidermis contains numerous labelled cells in suprabasal and external layers, indicating cell accumulation from more proximal epidermis. Cell proliferation dilutes the label, and keratinocytes take 8 days to migrate into corneous layers. In healing limbs, labelled cells remain sparse from 14 to 22 days of regeneration in wound epidermis and repairing tissues and little labelling dilution occurs indicating low cell proliferation for local tissue repair but not distal growth. Labelled cells are present in epidermis, intermuscle and peri-nerve connectives, bone periosteum, cartilaginous callus and sparse fibroblasts, leading to the formation of a scarring outgrowth. Resident stem cells and dedifferentiation occur when stump tissues are damaged.     

Appearance of tenascin in healing skin of the mouse: possible involvement in seaming of wounded tissues

Distribution of the extracellular matrix glycoprotein tenascin during wound healing in mouse skin was studied immunohistochemically. Within 24 hours after wounding, and preceding the formation of granulation tissue, tenascin appeared in the basement membranes beneath epidermis and hair follicles adjacent to the wound edges and in the wounded edges of cutaneous muscle layer. Granulation tissue began to form in the wound space at about 1-2 days and was immediately covered by epidermis. Tenascin first appeared in the periphery of the granulation tissue beneath healing epidermis and around the wounded edges of cutaneous muscle layer. Then the tenascin-positive area extended into the inner region of granulation tissue. At about 5-7 days, all of the granulation tissue was intensely stained with anti-tenascin serum. Tenascin immunoreactivity decreased as granulation tissue was replaced with reconstructed dermal tissue at 7-14 days. In most cases, tenascin staining persisted longest in the dermis beneath the healing epidermis and at the juncture of healing edges of cutaneous muscle layer. It disappeared at about 10-14 days after wounding. These findings suggest that tenascin may play an important role in the seaming of wounded tissues.     

Epidermal-dermal tissue interactions between mutant foot skin and normal back skin: a comparison of the inductive capacities of scaleless low line and normal anterior foot dermis.

The inductive capacities of 9- to 16-day anterior foot dermis of scaleless low line and normal embryos were compared by recombining them with a common source of epidermis, i.e., 7-day normal back epidermis. Tissue recombinants were cultured as grafts to the chorioallantoic membrane (CAM). Both normal and scaleless low line dermis of 12 to 13 days of incubation began to lose their ability to elicit feather production in 7-day normal back epidermis. Normal foot dermis began to elicit scale production at 12 to 13 days, whereas scaleless low line anterior foot dermis maintained feather production at a low level. It is inferred that without being associated with scale placode formation, scaleless low line anterior foot dermis does not acquire specific inductive capacities related to the production of an outer scale surface in the overlying epidermis. Feather placodes do not function as surrogates of scale placodes. The difference between normal and scaleless low line anterior foot dermis in terms of specific inductive capacities related to scale production is interpreted as a secondary effect of the action of the scaleless allele in interfering with scale placode formation in the scaleless low line anterior foot epidermis.     

EPIDERMAL REGENERATION AFTER CELLOPHANE TAPE STRIPPING OF HAIRLESS MOUSE SKIN

After repeated applications of cellophane tape to the dorsal skin of hairless mice, the proliferative response in the treated epidermis was estimated by three different methods. The mitotic rate was determined in the interfollicular epidermis using the Colcemid technique, and the DNA synthetic activity was estimated after ³H-thymidine injection by counting labelled interfollicular cells in autoradiographs and by determining the specific activity of epidermal DNA. An initial 40–50% inhibition of DNA synthesis and mitosis was followed by an increase in the labelling index and the mitotic rate 8–10 hr after tape stripping. By 24 hr, peak values 5–6 times the controls were attained for both parameters. The labelling index and the mitotic rate were nearly normal at 3–4 days, but a second small peak was seen on day 5. Normal values were found on days 6 and 8. A similar pattern of response was found biochemically, but the peak of DNA specific activity was much broader and the extent of the increase was only about half as great as the increase in the labelling index. Possible reasons for these differences are discussed.     

Ultraviolet B irradiation induces epidermal regeneration with rapidly cycling cells

The left flank of hairless mouse skin was irradiated with a minimal erythema dose of ultraviolet B (UVB) light at 297 nm (25 mJcm-2), while the right flank served as untreated control. The alterations in epidermal growth kinetics induced by this UVB dose were studied with the percentage of labelled mitoses (PLM) technique during the period of increased proliferation. Thirty hours after irradiation, when a large cohort of cells appears in S phase, each animal was injected intra-peritoneally with 50 microCi tritiated thymidine [( 3H]-TdR). The number of labelled basal and suprabasal cells, as well as their localization in epidermis were registered in histological sections at short intervals up to 48 h after the [3H]-TdR pulse. Labelled mitoses were also counted in the same specimens. The results showed a four-fold increase of the high initial number of labelled cells in UVB-exposed epidermis within 18 h of the pulse injection, and a six-fold increase after 36 h. In control epidermis, where the starting value of the labelling index was much lower, there was only a three to four-fold increase in the number of labelled cells during the period studied. The PLM and the labelling index data were consistent with an average cell cycle time of approximately 10-12 h for UVB-exposed cells, in contrast to about 30 h for the fastest cycling population in control epidermis. The PLM curve also indicated a prolonged S phase duration in UVB-exposed epidermis compared with controls. In addition, labelled cells were seen in the suprabasal layer as early as 6 h after the [3H]-TdR injection and within 36 h labelled cells had reached the outermost layer of nucleated cells, indicating a reduced transit time through epidermis. The present study shows that a minimal erythema dose of UVB light at 297 nm induced a period of increased transit time through the S phase, combined with rapid cell proliferation, leading to an overall shortening of the epidermal cell cycle time. The cohort of cells labelled with [3H]-TdR 30 h after irradiation seemed to proceed as a wave of partially synchronized cells through the cell cycle for more than two rounds, which is comparable with the cell kinetic perturbations observed in regenerating mouse epidermis.     

The fine structure of wound repair in an insect (Rhodnius prolixus)

The cells surrounding a wound in the integument of Rhodnius adults show an increase in RNA content, cytochrome oxidase and esterase activity. An excision in the integument is filled by blood which coagulates and is tanned into an insoluble membrane. The basement membrane of the adjoining epidermis acts as a self-sealing membrane and contracts to cover the excision. The epidermis is attached to the cuticle by the subcuticular layer which it resorbs and by pore canal filaments which are left behind as it migrates. The epidermis migrates as a sheet in contact with the cuticle then with the coagulated blood and basement membrane which cover the excision. Blood cells migrate individually into an excision and do not adhere to a surface in the process. Microtubules cannot be identified with movement. Both epidermal and blood cells remove the cells killed by wounding as evidenced by the appearance of coated vesicles and phagocytic bodies in both cell types. The reconstituted integument consists of a surface membrane in which the layers of the epicuticle are not distinguishable, a nonlamellate cuticle secreted by an epidermis which also appears to secrete the new basement membrane.     

Use of retinoic acid for the analysis of dermal-epidermal interactions in the tarsometatarsal skin of the chick embryo

Feet of chicks are normally covered with scales. Injection of retinoic acid into the amniotic cavity of 10-day chick embryos causes the formation of feathers on the foot scales. To elucidate whether retinoic acid affects primarily the epidermis or the dermis, heterotypic dermal-epidermal recombinants of tarsometatarsal skin were tested as to their morphogenetic capacity, when grafted to the chick chorioallantoic membrane. Recombinants involving treated epidermis and untreated dermis formed feathered scales, while the reverse recombinants of untreated epidermis and treated dermis led to the formation of scales only. Likewise the association of treated tarsometatarsal dermis with untreated epidermis from a non-appendage-forming region (the midventral apterium) resulted in the formation of scales only. These results show that retinoic acid affects primarily the epidermis. Further insight into the mechanism of dermal-epidermal interaction was gained by heterotopic recombinations of early (8.5- and 10-day) untreated tarsometatarsal dermis with epidermis from the midventral apterium. These recombinants formed scales, proving that tarsometatarsal dermis is endowed with scale-forming properties as early as 8.5 days of incubation. Finally, it is concluded that retinoic acid acts on the chick foot epidermal cells by temporarily inhibiting their scale placode-forming properties, allowing their latent feather placode-forming properties to be expressed.     

Ultraviolet B irradiation induces epidermal regeneration with rapidly cycling cells

Abstract. The left flank of hairless mouse skin was irradiated with a minimal erythema dose of ultraviolet B (UVB) light at 297 nm (25 mJcm^-2), while the right flank served as untreated control. The alterations in epidermal growth kinetics induced by this UVB dose were studied with the percentage of labelled mitoses (PLM) technique during the period of increased proliferation. Thirty hours after irradiation, when a large cohort of cells appears in S phase, each animal was injected intra-peritoneally with 50 /iCi tritiated thymidine ([³H]-TdR). The number of labelled basal and suprabasal cells, as well as their localization in epidermis were registered in histological sections at short intervals up to 48 h after the [³H]-TdR pulse. Labelled mitoses were also counted in the same specimens. The results showed a four-fold increase of the high initial number of labelled cells in UVB-exposed epidermis within 18 h of the pulse injection, and a sixfold increase after 36 h. In control epidermis, where the starting value of the labelling index was much lower, there was only a three to four-fold increase in the number of labelled cells during the period studied. The PLM and the labelling index data were consistent with an average cell cycle time of approximately 10–12 h for UVB-exposed cells, in contrast to about 30 h for the fastest cycling population in control epidermis. The PLM curve also indicated a prolonged S phase duration in UVB-exposed epidermis compared with controls. In addition, labelled cells were seen in the suprabasal layer as early as 6 h after the [³H]-TdR injection and within 36 h labelled cells had reached the outermost layer of nucleated cells, indicating a reduced transit time through epidermis. The present study shows that a minimal erythema dose of UVB light at 297 nm induced a period of increased transit time through the S phase, combined with rapid cell proliferation, leading to an overall shortening of the epidermal cell cycle time. The cohort of cells labelled with [³H]-TdR 30 h after irradiation seemed to proceed as a wave of partially synchronized cells through the cell cycle for more than two rounds, which is comparable with the cell kinetic perturbations observed in regenerating mouse epidermis.     

Ultrastructural analysis between fetal and adult wound healing process of marsupial opossum skin

The opossum delivers a newborn baby equivalent to tremature fetus state by postpregnancy. The peculiarity is advantageous for studies of fetus, because operations to take out fetus from the uterus of a mother are not necessary. When mammalian skin is wounded by full-thickness excision, fetal and adult wound healing processes differ. Fetal-type wound healing does not leave a scar. However, studies of how the fetal wound healing process differs in detail from the adult type are not advanced. We first observed the normal skin development of the gray short-tailed opossum (Monodelphis domestica) using an electron microscope. As for normal skin, an epidermis became multi-layered, and thickened from birth through to 7 days after birth. The quantity of extracellular matrix of the dermis increased thereafter, and several types of cells were found in the dermis. To examine the wound healing, we used material from a 1 day-old newborn baby, and from another 15 days after birth, and compared the wound healing style morphologically. Differences in the constitution of cells and fine structures of the skin were observed, it was obviously suggested that change in the wound healing style from fetal-type to adult-type occurred between 1 to 15 days after birth.     

Cutaneous wound healing in the sea cucumber, Thyone briareus

Wound healing in the integument of the sea cucumber, Thyone briareus, was studied for up to 50 days after inflicting wide excisional wounds and for 14 days after producing incisional wounds. Rapid re-epithelialization of the wound was effected by the migration of epidermal cells and pigment cells from the periphery of the wound margin. This occurred without apparent evidence of concomitant mitotic activity. Dermal wound healing was completed by the fourteenth day in the incision wounds but occurred very slowly in the broad excision wounds. Morula cells seem to be involved in both epidermal and dermal wound healing, although their precise role is unknown. In excisional wounds the integument was never completely restored to its normal appearance during 50 days of observation.     

Expression of the WE3 antigen in newt epithelium originating from subcutaneous grafts of skin

mAb WE3 recognizes an antigen that is developmentally regulated in the wound epithelium of regenerating newt limbs. The antigen is precociously expressed when pieces of WE3-negative wound epithelium are grafted subcutaneously (Tassava et al.: Recent Trends in Regeneration Research. New York: Plenum Publishing Co., pp. 37-49, 1989). In the present study, we investigated whether the WE3 antigen is expressed in epidermis of subcutaneous grafts of skin. Small pieces of limb skin were grafted into small tunnels in the lower jaw, limb, and tail, oriented either the same as (epidermis facing out) or opposite to (epidermis facing in) the orientation of the host skin. In most cases, the epithelium migrated from the graft along the wounded surface of the tunnel, closed onto itself, and formed a multilayered "emigrant" epithelium. Infrequently, the migrating epithelium combined with the wound epithelium of the insertion wound. In no case did the epithelium migrate over the cut edge of the grafted dermis. Reactivity to mAb WE3 was first seen at 4 days after grafting, when the migrating epithelium had almost closed over onto itself. By 6 days and thereafter, the entire emigrant epithelium was reactive to mAb WE3. While initially restricted to the emigrant epithelium, at 10 days after grafting and thereafter, reactivity was also seen in the epidermis that remained in contact with the dermis. Expression of the WE3 antigen was not influenced by the orientation of the graft nor by the graft site. The results show that, compared to amputated limbs, the epithelium originating from these grafts precociously expresses the WE3 antigen. Also, epidermis of grafted skin is capable of expressing the WE3 antigen.     

Distribution of S-phase cells during the regeneration of Drosophila imaginal wing discs

We investigated the distribution of S-phase cells during regeneration of the imaginal wing disc of Drosophila melanogaster following excision of 30 degrees, 90 degrees, and 150 degrees sectors of tissue. The fragments were cultured in adult abdomens for 1-5 days, labeled in vitro with tritiated thymidine, serially sectioned, and subjected to autoradiography. There was negligible thymidine incorporation in unoperated controls and in the undamaged parts of the operated discs, indicating that DNA synthesis in undamaged tissue is terminated during the first day of the culture period. Almost all of the fragments from which tissue had been removed, as well as controls which were simply cut without the removal of any tissue, showed a cluster of labeled cells (blastema) even after only 1 day of culture. The blastemas in control discs were short-lived, with over 50% of these discs showing no blastema by the third day in culture. Blastemas in discs from which sectors were removed were more persistent; the time at which 50% of the fragments no longer showed a blastema was 4 days for the -30 degrees fragments, 5 days for the -90 degrees fragments, and greater than 5 days for the -150 degrees fragments. The average blastema size, measured as number of labeled cells, was directly related to the amount of tissue removed, and in most cases did not change significantly during the culture period. Both wound edges incorporated tritiated thymidine initially and the S-phase cells remained tightly clustered throughout regeneration; maximum blastema width varied from about 8 to 25 cell diameters. The results are consistent with the idea that regenerative cell proliferation is stimulated and maintained by positional information discontinuities, and terminated when these discontinuities are resolved by the addition of an appropriate number of new cells.     

Short term cultivation of isolated barley roots and their mitotic activity

Roots were excised from barley embryos cultivated in the complete liquid nutrient solution and cultivated in the same nutrient solution separately. The excised roots continued their growth but a progressive decrease in the growth rate was observed. There was a considerable short-term drop of the mitotic activity immediately after excision, which was followed by a compensatory increase and then equilibrium was reached 12 h after excision. During the next at least three days, the mitotic index of isolated barley roots varied between 5–6.5%, which is slightly lower than the mitotic index of the root meristems of isolated barley embryos under identical conditions. The mitotic cycle index of isolated barley roots and the size of the root meristem later decreased gradually.     

Re‐epithelialization of large wound in paedomorphic and metamorphic axolotls

Axolotls (Ambystoma mexicanum ) may heal their skin wounds scar‐free in both paedomorphs and metamorphs. In previous studies on small punch skin wounds, rapid re‐epithelialisation was noted in these two axolotl morphs. However, large wound size in mammals may affect wound healing. In this study, large circumferential full thickness excision wounds on the hind limbs were created on juvenile paedomorphic and metamorphic axolotls. The results showed re‐epithelialisation was more quickly initiated in paedomorphs than in metamorphs after wounding. The migrating rate of epidermis on the wound bed was faster in paedomorphs than in metamorphs and thus completion of re‐epithelialisation was faster in paedomorphs than in metamorphs. Within these re‐epithelialisation periods, neither basement membrane nor dermis was reformed. Epidermal cell proliferation was detected by EdU‐labelling technique. In the normal unwounded skin, epidermal proliferation rate was higher in paedomorphs than in metamorphs. After wounding, the epidermal proliferation rate was significantly lower in the migrating front on the wound bed than in the normal skin in paedomorphs. The EdU‐labelling rate between normal skin and migration front was not different in metamorphs. Lacking of more proliferating epidermal cells on the wound bed indicated that the new epidermis here derived rather from migrating epidermal cells than from cell proliferation in situ. In conclusion, re‐epithelialisation in the large wound might be fully completed in both morphs despite it was initiated earlier and with faster rate in paedomorphs than in metamorphs. The new epidermis on the wound bed derived mainly from cell migration than by cell proliferation in the re‐epithelialisation period. J. Morphol. 278:228–235, 2017. © 2016 Wiley Periodicals,Inc.     

Mitotic and Labelling Activity In Normal Human Epidermis In Vivo

Labelling and mitotic indices were studied in the epidermis of twenty-eight young men. A mean labelling index of 5.5% was found from the whole study and a mean mitotic index of 0.06%. Mitotic index particularly was extremely variable; indices between 0.002 and 0.438% were found in individual biopsies. In the first two of three experiments in which mitotic index at 09.00 hours was compared with that at 15.00 hours, significant differences were found (15.00 hours > 09.00 hours by a factor of 2.6, P < 0.001). However, in the third such experiment no such difference was found, suggesting that the timing and occurrence of diurnal rhythms of mitotic activity may not be consistent in normal human epidermis. In the one experiment in which it was investigated, a significantly higher mitotic index was found at 21.00 hours compared to 09.00 and 15.00 hours. Labelling index did not vary significantly at 09.00, 15.00 or 21.00 hours. However, labelling index did show a significant pattern of change over a 12-month period in two groups of subjects; peaks of labelling were seen in July and troughs in January. Very high ratios of labelled: mitotic cells were found, the median ratio for the whole study being ninety-eight labelled: one mitotic cell. This finding supports the possibility that not all labelled cells subsequently go on to divide in normal human epidermis.     

Promotive effects of a silk film on epidermal recovery from full-thickness skin wounds

We examined the effects of the transparent fibroin film (silk film) on full-thickness skin wounds. Full-thickness dermatotomies (15 mm x 9 mm) were prepared on the dorsal wall of CRJ:CD-1 nu/nu (ICR nu/nu) mice. The area of the wounds dressed with silk film was reduced to 10% of that made by the dermatotomy 14 days after the dermatotomy and were covered with regenerated epidermis 21 days after the dermatotomy. In contrast, less recovery and epidermal regeneration were found 14 days after dermatotomy in the wounds dressed with a conventional hydrocolloid dressing (Duro Active). Furthermore, only partial incomplete epidemal growth was obtained 21 days after dermatotomy. Most importantly, the healing time of wounds dressed with silk film was 7 days shorter than those dressed with DuoActive dressing. The silk film showed an almost similar or slightly better promotive effect as the lyophilized porcine dermis (Alloask D), which is used as a dressing for burns, ulcers, and decubitis. Histologic findings revealed that there was greater collagen regeneration and less inflammation and neutrophil-lymphocyte infiltration of the wounds dressed with silk film than with DuoActive dressing. It is clear that regeneration of the epidermis and dermis of the wound beds covered with silk film was faster than with DuoActive dressing. Finally, silk film is easily obtainable, sterilizable, and transparent, and it allows easy observation of tissue recovery. Therefore, silk film offers advantages over other dressings and may be clinically useful for wound treatment.     

Epidermal-dermal tissue interactions between mutant and normal embryonic back skin: site of mutant gene activity determining abnormal feathering is in the epidermis.

The site of the scaleless gene's activity in the development of abnormal feathers was determined by reciprocally recombining epidermis and dermis between normal and scaleless chick embryos and culturing the recombinants for seven days on the chorioallantoic membrane. When recombined with a common dermal source, feather development is enhanced by scaleless high line as compared to scaleless low line epidermis. Against a common responding tissue, 7-day normal back epidermis, significant differences were not found in feather inducing ability between normal, scaleless high line and scaleless low line dermis. It was concluded that, in relation to abnormal feathering, these tissue interactions reveal that the site of the scaleless gene's activity is the epidermis. A model of tissue interaction in the development of normal and abnormal feathers is presented. According to the model, the focus of the scaleless mutation and the genes accumulated by selection for high or low feather numbers is the epidermis, the effect being that the reactivity of the epidermis to dermal stimuli is altered. Subsequently, the epidermis controls the morphogenetic organization of the dermis. The scaleless dermis is presumed to contain normal positional information for the determination of feather structure and pattern.