Sostdc1 defines the size and number of skin appendage placodes

Mammary glands and hair follicles develop as ectodermal organs sharing common features during embryonic morphogenesis. The molecular signals controlling the initiation and patterning of skin appendages involve the bone morphogenetic proteins and Wnt family members, which are commonly thought to serve as inhibitory and activating cues, respectively. Here, we have examined the role of the Bmp and Wnt pathway modulator Sostdc1 in mammary gland, and hair and vibrissa follicle development using Sostdc1-null mice. Contrary to previous speculations, loss of Sostdc1 did not affect pelage hair cycling. Instead, we found that Sostdc1 limits the number of developing vibrissae and other muzzle hair follicles, and the size of primary hair placodes. Sostdc1 controls also the size and shape of mammary buds. Furthermore, Sostdc1 is essential for suppression of hair follicle fate in the normally hairless nipple epidermis, but its loss also promotes the appearance of supernumerary nipple-like protrusions. Our data suggest that functions of Sostdc1 can be largely attributed to its ability to attenuate Wnt/β-catenin signaling.     

Characterization of Wnt gene expression in developing and postnatal hair follicles and identification of Wnt5a as a target of Sonic hedgehog in hair follicle morphogenesis

Mutations in WNT effector genes perturb hair follicle morphogenesis, suggesting key roles for WNT proteins in this process. We show that expression of Wnts 10b and 10a is upregulated in placodes at the onset of follicle morphogenesis and in postnatal hair follicles beginning a new cycle of hair growth. The expression of additional Wnt genes is observed in follicles at later stages of differentiation. Among these, we find that Wnt5a is expressed in the developing dermal condensate of wild type but not Sonic hedgehog (Shh)-null embryos, indicating that Wnt5a is a target of SHH in hair follicle morphogenesis. These results identify candidates for several key follicular signals and suggest that WNT and SHH signaling pathways interact to regulate hair follicle morphogenesis.     

Hoxa4 expression in developing mouse hair follicles and skin

We have examined the expression of the Hoxa4 gene in embryonic vibrissae and developing and cycling postnatal pelage hair follicles by digoxigenin-based in situ hybridization. Hoxa4 expression is first seen in E13.5 vibrissae throughout the follicle placode. From E15.5 to E18.5 its expression is restricted to Henle's layer of the inner root sheath. Postnatally, Hoxa4 expression is observed at all stages of developing pelage follicles, from P0 to P4. Sites of expression include both inner and outer root sheaths, matrix cells, and the interfollicular epidermis. Hoxa4 is not expressed in hair follicles after P4. Hoxb4, however, is expressed both in developing follicles at P2 and in catagen at P19, suggesting differential expression of these two paralogous genes in the hair follicle cycle.     

Appearance of hair follicle-inducible mesenchymal cells in the rat embryo

Rat vibrissa follicle morphogenesis starts around 13 days of gestation. By day 14 mesenchymal cells have already aggregated as 'condensations' beneath the initial hair bud. Some of the mesenchymal cells will form a dermal papilla, having profound effects on hair follicle formation. The appearance of follicle-inducing mesenchymal cells in the process of vibrissa follicle development was examined. Mesenchymal cells were isolated from the developing site of vibrissa follicles at 13 days or at later stages and amplified in mass culture, harvested and transplanted in association with the epithelium. It was demonstrated that 13-day mesenchymal cells did not induce any hair bulbs but those from 14 days or later stages could induce hair-producing new bulbs or new follicles depending on the association with the follicle epithelium or with the glabrous sole epidermis of the adult rats, respectively. Further, clones having hair bulb-inducing ability were obtained from 14- and 15-day mass-cultured mesenchymal cells. Based on these and other results, it was concluded that mesenchymal cells having follicle-inducing ability are present at least by 14 days in the future whisker pad region. This suggests that the differentiation of the dermal papilla cells must start before the initial hair bud stage.     

Drapc1 expression during mouse embryonic development

We identified the mouse homolog of human DRAPC1 (APCDD1) gene, shown to be a target of Wnt/beta-catenin signaling pathway in cancer cell lines. Analysis of its spatiotemporal expression in mouse embryos from E7.5 to E14 showed that Drapc1 is expressed during development of the extraembryonic structures, nervous system, vascular system and inner ear. In addition, Drapc1 is expressed in the mesenchyme of several developing organs at sites of epithelio-mesenchymal interactions. Drapc1 expression was also found in the hair follicles of the adult mouse skin. Similarity of Drapc1 expression pattern to location of active beta-catenin in developing mouse embryo further suggests that mouse Drapc1 is a novel in vivo target gene of Wnt/beta-catenin signaling pathway.     

Induction of follicle formation and hair growth by vibrissa dermal papillae implanted into rat ear wounds: vibrissa-type fibres are specified.

Adult vibrissa follicle dermal papillae have the capacity to induce hair growth and follicle formation when associated with epidermis from various sources. However, the range of conditions under which hair follicle induction will take place has not been established. The question of whether or not the adult papilla carries information to impose fibre-type specificity has also not been fully answered. This study describes how the implantation of isolated papillae into small incisional cuts on the rat ear pinna resulted in the subsequent emergence of abnormally large hair fibres from the wound sites. Many of these hairs were found to display vibrissa-type characteristics. Histological observations indicated that the papillae had interacted with the edges of the wound epidermis to produce new, and particularly large follicles, while immunohistochemical staining revealed that early follicle construction was accompanied by a profusion of the basement membrane constituents laminin and type IV collagen in the subjacent dermis. These findings show that adult rat papillae retain the capacity, as displayed by embryonic dermis, to determine vibrissa specificity in induced follicles.     

Urokinase plasminogen activator (uPA) is a positive regulator of outer root sheath keratinocyte proliferation

Urokinase plasminogen activator (uPA), a serine proteinase, is important in the development and epidermal wound healing, and seems to play a regulatory role in the proliferation of mouse epidermal keratinocytes (KC). In the present study, we found detectable uPA expression in outer root sheath (ORS) KC in the early anagen phase in mouse vibrissa follicles, but not in the late anagen or in the telogen and categen phases. uPA was also detected in ORS KC cultured from neonatal mice vibrissa. Specific exogenous inhibitors of uPA, amiloride and uPA antibody, significantly reduced the proliferation of ORS KC. Thus uPA is consistently elevated in the hyperproliferative hair follicle KC, and inhibition of the enzyme decreases hair follicle KC proliferation. We deduce that uPA is a very important mediator of the hair follicle cycle because its activity correlates with ORS KC proliferation.     

新生小鼠不同部位皮肤毛囊早期发育差异的比较

目的观察出生后小鼠不同部位皮肤毛囊早期发育生长差异及细胞色素C的表达分布。方法对新生1~9日龄的KM小鼠背部、尾部和触须部皮肤取材,进行HE染色,用二步法免疫组织化学对组织进行细胞色素C进行表达分布检测。结果新生小鼠不同部位皮肤毛囊发育差异很大,这种差异不仅体现在形态差异上,而发育时间的差异也十分明显。小鼠出生后背部皮肤和尾部皮肤的毛囊发育都经过了一个非线性的发育和生长期,过了非线性的发育和生长期才开始快速生长,相比较尾部发育略迟于背部。触须部毛囊发育特征和背部尾部差异很大,一出生便可看到较成熟的触毛,没有经过稳定期便开始发育。结论通过形态学比较,结合CytC表达分布水平,发现新生小鼠不同部位皮肤毛囊早期发育存在形态和时间上的差异。     

Hairs and vibrissae in the Rhinocerotidae

Evidence is reviewed and observations are submitted concerning the occurrence and distribution of body hair in rhinoceroses. Absence of externally visible hair is shown to be not necessarily indicative of absence of hair follicles and to be part of a morphological cooling mechanism necessitated by the dynamics of the large body. Eyelashes are shown to be present on the lower eyelid of three species at least. The post-natal absence of all groups of facial vibrissae is confirmed for all rhinoceros forms, but a genal vibrissa is recorded for a Diceros foetus. Observations are submitted upon the hitherto undescribed histology of Diceros skin.