A key initial event in hair follicle morphogenesis is the localised thickening of the skin epithelium to form a placode, partitioning future hair follicle epithelium from interfollicular epidermis. Although many developmental signalling pathways are implicated in follicle morphogenesis, the role of epidermal growth factor (EGF) and keratinocyte growth factor (KGF, also known as FGF7) receptors are not defined. EGF receptor (EGFR) ligands have previously been shown to inhibit developing hair follicles; however, the underlying mechanisms have not been characterised. Here we show that receptors for EGF and KGF undergo marked downregulation in hair follicle placodes from multiple body sites, whereas the expression of endogenous ligands persist throughout hair follicle initiation. Using embryonic skin organ culture, we show that when skin from the sites of primary pelage and whisker follicle development is exposed to increased levels of two ectopic EGFR ligands (HBEGF and amphiregulin) and the FGFR2(IIIb) receptor ligand KGF, follicle formation is inhibited in a time-and dose-dependent manner. We then used downstream molecular markers and microarray profiling to provide evidence that, in response to KGF and EGF signalling, epidermal differentiation is promoted at the expense of hair follicle fate. We propose that hair follicle initiation in placodes requires downregulation of the two pathways in question, both of which are crucial for the ongoing development of the interfollicular epidermis. We have also uncovered a previously unrecognised role for KGF signalling in the formation of hair follicles in the mouse.

There is considerable interest in the potential for measuring cortisol in hair as a means of quantifying stress responses in human and non-human animals. This review updates the rapid advancement in our knowledge of hair cortisol, methods for its measurement, its relationship to acute and chronic stress, and its repeatability and heritability. The advantages of measuring cortisol in hair compared with other matrices such as blood, saliva and excreta and the current theories of the mechanisms of cortisol incorporation into the fibre are described. Hair cortisol as a measure of the physiological response to stress in a variety of species is presented, including correlations with other sample matrices, the relationship between hair cortisol and psychosocial stress and the repeatability and heritability of hair cortisol concentrations. Current standards for the quantification of hair cortisol are critically reviewed in detail for the first time and gaps in technical validation of these methods highlighted. The known effects of a variety of sources of hair cortisol variation are also reviewed, including hair sampling site, sex, age and adiposity. There is currently insufficient evidence to conclude that cortisol concentration in hair accurately reflects long-term blood cortisol concentrations. Similarly, there is a lack of information surrounding the mechanisms of cortisol incorporation into the hair. This review highlights several directions for future research to more fully validate the use of hair cortisol as an indicator of chronic stress.

Clostridial infection of the intestine can result in necrotic enteritis (NE), compromising production and health of poultry. Mucins play a major role in protecting the intestinal epithelium from infection. The relative roles of different mucins in gut pathology following bacterial challenge are unclear. This study was designed to quantify the expression of mucin and mucin-related genes, using intestinal samples from an NE challenge trial where birds were fed diets with or without in-feed antimicrobials. A method for quantifying mucin gene expression was established using a suite of reference genes to normalize expression data. This method was then used to quantify the expression of 11 candidate genes involved in mucin, inflammatory cytokine, or growth factor biosynthesis (IL-18, KGF, TLR4, TFF2, TNF-α, MUC2, MUC4, MUC5ac, MUC5b, MUC13, and MUC16). The only genes that were differentially expressed in the intestine among treatment groups were MUC2, MUC13, and MUC5ac. Expression of MUC2 and MUC13 was depressed by co-challenge with Eimeria spp. and Clostridium perfringens. Antimicrobial treatment prevented an NE-induced decrease in MUC2 expression but did not affect MUC13. The expression of MUC5ac was elevated in birds challenged with Eimeria spp./C. perfringens compared with unchallenged controls and antimicrobial treatment. Changes to MUC gene expression in challenged birds is most likely a consequence of severe necrosis of the jejunal mucosa.

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Lamb mortality represents reproductive wastage and an animal welfare concern. While lambs are thought to be at a thermogenic advantage following birth in comparison to other species, death from exposure can still be a major contributor to lamb mortality, largely because of the inclement conditions often prevailing at lambing. For this reason, thermogenesis has been studied extensively in neonatal lambs. Heat is produced in the neonatal lamb by shivering and non-shivering thermogenesis. The latter is heat generated by metabolism of brown adipose tissue (BAT) found largely in the thorax and peri-renal areas of the newborn lamb. Brown adipose tissue differs from normal adipose tissue in that it contains densely packed mitochondria, a high cytochrome c content and a vast vascular network. Heat is generated in BAT by uncoupling of the proton conductance mechanism from ATP production, resulting in heat production instead of stored energy. The ability of lambs to resist cooling differs among individuals and this is likely to be due to both genetic and phenotypic factors. The heritability of cold resistance is moderate-to-high and polymorphic gene markers associated with energy homeostasis and cold-related mortality have been identified. Additionally, several aspects of the phenotype of the lamb have been associated with cold resistance. Most relate to properties of the coat, skin and bodyweight, the latter being particularly important, presumably through effects on surface area to volume ratios and subsequent heat loss. The ability of the neonate to achieve the transition from intra- to extra-uterine life has been termed physiological maturity and is associated with the ability to activate appropriate neuro-endocrinological and behavioural changes that are consistent with homeostasis of energy metabolism. Ways to alter physiological maturity of the lamb, such as nutrition, pharmacology and genetic selection, have been identified, and while these show promising results with regards to thermoregulation, a key limitation of their application has been the lack of a repeatable, representative model of neonatal cold stress. An estimation of the non-shivering component potential of a lamb’s ability to thermoregulate can be derived from norepinephrine challenges, but more useful models of real-world cold stress are climate chambers or controlled water bath tests. Further use of repeatable test models such as these with appropriate neuroendocrine and metabolic metrics will identify key components and markers of physiological maturity associated with lamb thermogenesis and survival.