N. M. Edwards

The role of activins and follistatins in skin and hair follicle development and function

Investigations of the signalling between epithelial and mesenchymal compartments of skin during hair follicle initiation in utero and hair cycling have revealed the importance of the TGFbeta superfamily in ectodermal organogenesis and morphogenesis. In particular the activins, their receptors and binding proteins such as follistatin, have been shown to be important regulators of cell proliferation, differentiation and apoptosis in hair follicle initiation, hair cycling, normal skin homeostasis and wound healing. Transgenic mice lacking various components of the activin signalling pathways display varying ectodermal pathologies including altered pelage hair follicle initiation. This review summarises the activin signal transduction pathways and the interactions between activins and other TGFbeta signalling systems during hair follicle formation, hair growth cycling, skin function and wound healing.

Phenotypic and genotypic analysis of a barebreech trait in Merino sheep as a potential replacement for surgical mulesing.

The potential for adopting a genetic solution to protect sheep from blowfly strike on the breech was investigated in a flock of sheep that contained several animals expressing a trait characterised by low wool coverage over the breech and through a wide channel from the anus to the udder or scrotum. A scoring system (1, bare to 5, woolly) was developed and used to determine the heritability of the trait and its phenotypic and genetic correlations with other traits of importance in a sheep enterprise. In comparison to animals with woolly breeches, the skin in the breech of animals with a low bareness score was characterised by a low density of follicles producing short, medullated fibres, with histological evidence of immune rejection and follicular atrophy. The bareness score of progeny was influenced by the score of their respective sires suggesting a strong genetic component. The heritability of bareness score was moderate to high (h2 = 0.45 ± 0.02, 0.53 ± 0.01 and 0.38 ± 0.02 at lamb, hogget and adult ages, respectively). The lactation status and age of ewes influenced their bareness score, resulting in a low repeatability (0.42) of the trait between ages in females. Genetic correlations between bareness score and most other economically important traits were low. The weight of belly wool and the weight of skirtings was genetically related to bareness score (rg = +0.52 and +0.48 respectively), indicating that animals with barer breeches tend genetically towards lighter belly wool weights and lower weight of skirtings at wool classing. Selection and breeding for bareness score should achieve relatively rapid progress towards fixing the trait in a flock and without adverse effects on other important traits. Caution should be exercised in extrapolating these results to other bloodlines and environments where genetic mechanisms or environmental influences may be different.

Wool fibre crimp is determined by mitotic asymmetry and position of final keratinisation and not ortho- and para-cortical cell segmentation.

Crimp, a distinguishing feature of sheep fibres, significantly affects wool value, processing and final fabric attributes. Several explanations for fibre bending have been proposed. Most concentrate on relative differences in the physicochemical properties of the cortical cells, which comprise the bulk of the fibre. However, the associations between cortical properties and fibre crimp are not consistent and may not reflect the underlying causation of fibre curvature (FC). We have formulated a mechanistic model in which fibre shape is dictated primarily by the degree of asymmetry in cell supply from the follicle bulb, and the point at which keratinisation is completed within the follicle. If this hypothesis is correct, one would anticipate that most variations in fibre crimp would be accounted for by quantitative differences in both the degree of mitotic asymmetry in follicle bulbs and the distance from the bulb to the point at which keratinisation is completed. To test this hypothesis, we took skin biopsies from Merino sheep from sites producing wool differing widely in fibre crimp frequency and FC. Mitotic asymmetry in follicle bulbs was measured using a DNA-labelling technique and the site of final keratinisation was defined by picric acid staining of the fibre. The proportion of para- to ortho-cortical cell area was determined in the cross-sections of fibres within biopsy samples. Mitotic asymmetry in the follicle bulb accounted for 0.64 (P < 0.0001) of the total variance in objectively measured FC, while the point of final keratinisation of the fibre accounted for an additional 0.05 (P < 0.05) of the variance. There was no association between ortho- to para-cortical cell ratio and FC. FC was positively associated with a subjective follicle curvature score (P < 0.01). We conclude that fibre crimp is caused predominantly by asymmetric cell division in follicles that are highly curved. Differential pressures exerted by the subsequent asymmetric cell supply and cell hardening in the lower follicle cause fibre bending. The extent of bending is then modulated by the point at which keratinisation is completed; later hardening means the fibre remains pliable for longer, thereby reducing the pressure differential and reducing fibre bending. This means that even highly asymmetric follicles may produce a straight fibre if keratinisation is sufficiently delayed, as is the case in deficiencies of zinc and copper, or when keratinisation is perturbed by transgenesis. The model presented here can account for the many variations in fibre shape found in mammals.

Transient treatment of pregnant Merino ewes with modulators of cortisol biosynthesis coinciding with primary wool follicle initiation alters lifetime wool growth

The economically important characteristics of the adult fleece of Merino sheep, such as increases in clean fleece weight, fibre length, fibre diameter and crimp characteristics are determined during critical phases of fetal development of the skin and its appendages. Genetics plays a major role in the development of traits, but the maternal uterine environment could also influence development. Treatment of pregnant ewes with cortisol and its analogues has previously been shown to produce changes in wool follicle morphology. The aim of this study was to determine the effect of transient manipulation of maternal cortisol status during critical phases of wool follicle initiation and development in utero. From Days 55–65 post-conception, singleton-bearing Merino ewes were treated with metyrapone (cortisol inhibitor) or betamethasone (cortisol analogue). Lambs exposed to metyrapone in utero were born with hairier birthcoats than the control or betamethasone treatment groups (P < 0.05), displayed a 10% increase in staple length and a reduction in crimp frequency for the first three shearings (P < 0.05). Co-expression network analysis of microarray data revealed up-regulation of members of the transforming growth factor-β and chemokine receptor superfamilies, gene families known to influence hair and skin development. These experiments demonstrate that presumptive transient manipulation of maternal cortisol status coinciding with the initiation of fetal wool follicle development results in long-term alteration in fleece characteristics, namely fibre length and fibre crimp frequency. These results indicate it is possible to alter the lifetime wool production of Merino sheep with therapeutics targeted to gene expression during key windows of development in utero.

Developmental programming: a new frontier for the poultry industry?

Increasing evidence that the maternal environment influences the programming of developing embryos and fetuses through epigenetic mechanisms has significant potential application in the broiler industry. The broiler breeder hen is subjected to restricted-feeding regimes to maximise egg quantity and quality, but the genetically high-intake potential of these birds makes this regime a stressful one. We propose that this stress is signalled to the developing embryo via changes in yolk composition as an evolutionary adaptation to changing environments, and that exposure to high levels of corticosteroids in ovo is associated with developmental reprogramming, which has effects on the behaviour, health and growth of the progeny. The present paper describes some preliminary results from a series of trials designed to elucidate the relationship between breeder hen diet and egg composition, and the growth, behaviour and immune function of the progeny. We conclude that manipulation of the breeder hen diet is an untapped opportunity to maintain the competitiveness of the chicken meat industry and further, that achieving improved productivity by this means may be compatible with improved animal welfare outcomes for the hen and her progeny.

The effects of short-term manipulation of thyroid hormone status coinciding with primary wool follicle development on fleece characteristics in Merino sheep

Thyroidectomy surgery performed late in gestation results in perturbations in wool follicle development in foetal sheep, showing the importance of thyroid hormones for wool follicle development. The aim of this study was to determine the influence of transient manipulation of thyroid hormone status at a time corresponding with foetal primary wool follicle initiation. Pregnant Merino ewes (n = 12 per treatment) were treated daily between gestational days 55 and 64 with control (vehicle), exogenous thyroxine (T4) or propylthiouracil (PTU), an inhibitor of T4 synthesis, and conversion to the active form of the thyroid hormone (triiodothyronine). There were no significant differences in birth weight, gestational lengths and birth coat scores of the resultant lambs. The total primary and secondary follicle densities were significantly lower in lambs exposed to exogenous T4 compared with other treatments (P < 0.05). However, the T4 group displayed a higher proportion of mature secondary follicles (reflected by increased mature secondary follicle densities and mature secondary/primary follicle ratios) than the other treatment groups (P < 0.05). The skin morphology of the lambs differed 12 months later, with the T4 group having significantly higher total follicle densities compared with the PTU group, largely attributed to increased mature and total secondary follicle densities. However, this increase in wool follicle densities did not translate to differences in the fleece yields and weight, fibre diameter, staple lengths or any other fibre parameters. This study showed that transient manipulation of thyroid hormone status during foetal primary follicle initiation does have long-term consequences on the morphology of wool follicles, in particular the maturity of secondary wool follicles.

Biological defleecing: intravenous infusion of amino acid mixtures lacking lysine and methionine creates a weakened zone in the wool staple, which is amenable to mechanical wool harvesting

Conventional shearing of sheep is labour-intensive, expensive and presents significant occupational health and safety risks. The only alternative at present is based on injection of epidermal growth factor, which severs the fibre at the follicle level. This technology cannot be used in pregnant animals and requires application of a net to retain the severed fleece. An alternative is to create a weakened zone within the wool staple, which would be sufficiently strong to retain the fleece on the sheep while a protective covering regrows, but sufficiently weak as to allow painless and automated removal of the fleece. We demonstrate that this approach is possible using mixtures of amino acids lacking lysine and methionine. Initially we demonstrate the relationships between staple strength, a subjective ‘harvestability’ score and a subjective ‘pain’ score, using fleeces from animals treated with varying levels of cortisol to create a wide range of strengths of wool attachment. We assigned a score to the ease with which we could manually break the staples, and also to the animal’s response to breaking the staples still attached to the skin. The relationships between these variables indicated that a staple was considered harvestable and could be removed with minimal skin flinch response at a staple strength of ~10–13 N/kTex. Staples within this range were then produced by intravenous infusion of mixtures of amino acids lacking in lysine and methionine for a 5-day period. The weak point was uniformly created across the entire fleece and when a prototype roller-pin device was applied to the weakened wool, it uniformly broke the fleece of the three sheep tested. The mode of action of the amino acid treatment on wool growth was studied. There was no effect of unbalanced amino acids on the rate of follicle bulb cell division, the number of active wool follicles, or the length of the keratinisation zone in the wool follicle. Fibre diameter was reduced by ~4 microns by treatment, and intrinsic fibre strength (strength relative to cross-sectional area of the wool fibres), was reduced by ~50%. Results of these trials are encouraging but further work is required to develop a practical, on-farm method of altering systemic amino acid supply and to design an automated, high-throughput system of severing the weakened wool.