I.—On the Developmental Processes in Mammary Glands and other Epidermal Structures

Balinsky, B. I.

doi:10.1017/s0080456800009224

Cited by 46 publications

(19 citation statements)

References 12 publications

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“…On the other hand, this fact is in keeping with the in vitro studies of the mouse breast model, in which hormones such as insulin, prolactin and aldosterone, unlike estrogen and progesterone, seem to be heavily involved in early growth [9,10]. On the other hand, low cell proliferation was also demonstrated in the mouse model, in which the mitotic index of the fetal breast gland turned out to be lower than that of the surrounding epidermis [6]. The puberal breast showed high ER and PR expression, which is probably the consequence of the intense hormonal stimulation to which the breast is exposed in this phase of growth.…”

Section: Discussionsupporting

confidence: 73%

Bio-morphological events in the development of the human female mammary gland from fetal age to puberty

et al. 2000

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Bio-morphological understanding of the developing human mammary glands may clarify some aspects of breast pathology, including cancer. In particular, some epidemiological data suggests that during fetal growth an altered intrauterine hormonal status, especially a change in estrogen status, could predispose to carcinogenesis. In an attempt to achieve new information on early breast growth, a series of developing human breasts have been analyzed, namely: 4 fetal breasts (28-32 weeks of gestational age), 7 infant breasts (7 h to 2 years) and 1 puberal breast (12 years). In addition to the morphological features, we studied the immunohistochemical expression of some markers involved in morphogenesis, such as MIB-1 for cell proliferation, bcl-2 for apoptosis control, CD34 for vasculogenesis, estrogen (ER) and progesterone (PR) receptors for hormonal profile, and smooth-muscle actin for myoepithelial differentiation. The results were as follows: (a) lobules, absent between 28 weeks and 2 days, were well evident at 2 years of age and at puberty; (b) myoepithelial cells appeared from 28 weeks onward and persisted later with no modification in quantity and distribution; (c) epithelial cell proliferation was constantly low; (d) in all breasts inner epithelial cells showed diffuse bcl-2 positivity, while basal myoepithelial-like cells were generally negative; (e) all breasts were well vascularized with two different patterns: periductal vascularization (PDV) and interductal vascularization (IDV), IDV being always present, whereas PDV was found only in infant breasts; (f) ER and PR were almost absent in fetal and infant breasts, while their expression was high in the epithelial cells of the puberal breast; (g) stromal cells had no hormonal receptors and were heterogeneous for proliferation and bcl-2 expression. Interestingly, two fetal breasts showed high proliferation and high ER expression, respectively, in their epithelial compartment. This could be the expression of an altered hormonal environment in utero, representing a basis for possible subsequent cancer initiation.

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Section: Discussionsupporting

confidence: 73%

Bio-morphological events in the development of the human female mammary gland from fetal age to puberty

et al. 2000

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“…We also demonstrate that Nrg3 regulates epithelial progenitor accretion without increasing epithelial mitosis. The limited epithelial proliferation detected cannot account for the observed increases in mammary primordial size that occur between E10.5 and E13.5 and influx of cells from the adjacent surface epithelium accounts for most increases in epithelial cell numbers within the nascent organ [15][16][17]. Our results indicate Nrg3 signals mediate the distribution of epithelial progenitor cells along the ventral thoracic flank at the time that they are thought to be locally migrating to form the MP.…”

Section: Alterations In Epithelial Progenitor Cell Distributions Inmentioning

confidence: 81%

“…As a result, much remains to be understood regarding the cellular and molecular mechanisms by which the initial MP is developed from the simple epithelium. It has been clearly established that a very low level of cell proliferation is detected within the mammary primordial epithelium during the initial stages of organ formation from E11 through E14 stages [15,16]. Previous studies have concluded that early mammary morphogenesis is primarily mediated via localized cell movements [15,17].…”

Section: Introductionmentioning

confidence: 99%

“…It has been clearly established that a very low level of cell proliferation is detected within the mammary primordial epithelium during the initial stages of organ formation from E11 through E14 stages [15,16]. Previous studies have concluded that early mammary morphogenesis is primarily mediated via localized cell movements [15,17]. It is not yet clear which signals mobilize the epithelial progenitors that are thought to locally migrate from along and near the mammary line to form the MP [1].…”

Section: Introductionmentioning

confidence: 99%

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Neuregulin-3Regulates Epithelial Progenitor Cell Positioning and Specifies Mammary Phenotype

Kogata

Oliemuller

Wansbury

et al. 2014

Stem Cells and Development

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Mutation of Neuregulin-3 (Nrg3) results in defective embryonic mammary gland development. Here, we investigate functions of Nrg3 signaling in embryonic mammary morphogenesis. Nrg3 regulates the distribution of epithelial progenitor cells within the presumptive mammary-forming region during early mammary morphogenesis. Basal and suprabasal epithelial cells are significantly smaller within the hypoplastic mammary primordium (MP) that forms in Nrg3 mutants, indicative of failure to acquire mammary epithelial cell (MEC) morphological phenotype. Activation of Erbb4 JM-a CYT-1, an Erbb4 isoform expressed in the developing MP, leads to MEC spreading and migration. Nrg3 promotes the accumulation of epithelial progenitor cells at the MP site in embryo explant cultures. Our results implicate Nrg3 signaling in mediating key events of mammary mesenchyme specification, including mesenchymal condensation, mitosis, and induction of mammary marker expression. Taken together, our results show Nrg3 has a major role in conferring specification of the mammary phenotype to both epithelial and mesenchymal progenitor cells.

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“…While the signals involved in this inductive event are unknown, the actual formation of the mammary ridge and bud does not appear to involve increased local epithelial proliferation insofar as the formation of the thickened mammary ridge proceeds too rapidly to be ex plained by cell proliferation [Balinsky, 1950: Propper, 1970, and the mitotic index of the early mammary anlagen is in fact lower than the surrounding epidermis [Balinsky, 1950]. Indeed, it has been postulated that the mesenchyme-induced formation of the mammary bud involves cell migration and change in cell shape [Balinsky.…”

Section: Discussionmentioning

confidence: 99%

Mammary Phenotypic Expression Induced in Epidermal Cells by Embryonic Mammary Mesenchyme

Cunha

Young

Christov

et al. 1995

Cells Tissues Organs

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The goal of this research was to establish methods for inducing mammary epithelial differentiation from nonmammary epithelium. For this purpose, mid-ventral or dorsal epidermis (skin epithelium; SKE) from 13-day rat or mouse embryos was associated with 13-day embryonic mouse mammary mesenchyme (mammary gland mesenchyme; MGM) (mouse MGM + rat or mouse SKE). The resultant MGM + SKE recombinants as well as controls (homotypic mouse mammary recombinants, homotypic mouse skin recombinants and mouse mammary mesenchyme by itself) were grafted under the renal capsule of syngeneic or athymic female nude mouse hosts. Most female hosts were induced to undergo lactogenesis by grafting an adult pituitary which elicited a state of hyperprolactinemia. Tissue recombinants of mouse MGM + rat or mouse SKE grown for 1 month in vivo formed a hair-bearing keratinized skin from which mammary ductal structures extended into the mesenchyme. The ducts were composed of columnar luminal epithelial cells as well as basal, actin-positive myoepithelial cells. When grown in pituitary-grafted hosts, the ductal epithelial cells expressed casein and α-lactalbumin as judged by immunocytochemistry. The expression of caseins in MGM + SKE recombinants was confirmed by Western blot. The epithelial cells in mouse MGM + rat SKE recombinants expressing milk proteins were shown to be rat cells while the surrounding connective tissue was composed of mouse cells based upon staining with Hoechst dye 33258. Using mammary-specific markers, these studies confirmed the earlier morphological studies of Propper and unequivocally demonstrated for the first time that embryonic mammary mesenchyme can induce morphological and functional mammary differentiation from nonmammary epithelium.

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I.—On the Developmental Processes in Mammary Glands and other Epidermal Structures

Cited by 46 publications

References 12 publications

Bio-morphological events in the development of the human female mammary gland from fetal age to puberty

Bio-morphological events in the development of the human female mammary gland from fetal age to puberty

Neuregulin-3Regulates Epithelial Progenitor Cell Positioning and Specifies Mammary Phenotype

Mammary Phenotypic Expression Induced in Epidermal Cells by Embryonic Mammary Mesenchyme

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