Abnormal Hair Development and Apparent Follicular Transformation to Mammary Gland in the Absence of Hedgehog Signaling

Gritli-Linde, Amel; Hallberg, K.; Harfe, Brian D.; Reyahi, Azadeh; Kannius-Janson, Marie; Nilsson, Jeanette; Cobourne, Martyn T.; Sharpe, Paul T.; McMahon, Andrew P.; Linde, Anders

doi:10.1016/j.devcel.2006.12.006

Cited by 81 publications

(70 citation statements)

References 34 publications

(25 reference statements)

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“…However, the level and/or timing of Shh expression might be an important effector. Suggestively, inhibition of Shh signaling resulted in glandular tissue formation in back skin, which otherwise harbors only hair follicles (Gritli-Linde et al, 2007). In addition, consistent with this notion, we found that Shh expression was very low in early sweat gland induction stages and then increased sharply during postnatal secretory coil formation .…”

Section: Shh Action: An Example Of Variable Involvement and Timing Insupporting

confidence: 76%

Involvement of Wnt, Eda and Shh at defined stages of sweat gland development

et al. 2014

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To maintain body temperature, sweat glands develop from embryonic ectoderm by a poorly defined mechanism. We demonstrate a temporal cascade of regulation during mouse sweat gland formation. Sweat gland induction failed completely when canonical Wnt signaling was blocked in skin epithelium, and was accompanied by sharp downregulation of downstream Wnt, Eda and Shh pathway genes. The Wnt antagonist Dkk4 appeared to inhibit this induction: Dkk4 was sharply downregulated in β-catenin-ablated mice, indicating that it is induced by Wnt/β-catenin; however, its overexpression repressed Wnt target genes and significantly reduced gland numbers. Eda signaling succeeded Wnt. Wnt signaling was still active and nascent sweat gland pre-germs were still seen in Eda-null mice, but the pre-germs failed to develop further and the downstream Shh pathway was not activated. When Wnt and Eda were intact but Shh was ablated, germ induction and subsequent duct formation occurred normally, but the final stage of secretory coil formation failed. Thus, sweat gland development shows a relay of regulatory steps initiated by Wnt/β-catenin -itself modulated by Dkk4 -with subsequent participation of Eda and Shh pathways.

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Section: Shh Action: An Example Of Variable Involvement and Timing Insupporting

confidence: 76%

Involvement of Wnt, Eda and Shh at defined stages of sweat gland development

et al. 2014

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“…40,50 The appearance of Gli2 in hepatocytic cells was surprising because during development and repair of other tissues, Hh ligand production is most conspicuous in epithelial cells and Hh target gene expression localizes in mesenchymal cells. 20,51,52 Following even mild acute or chronic injury to hepatocytes, however, we noted that expression of the Hh ligand, Ihh, and the Hh target, Gli2, tended to localize in very close proximity (and possibly colocalize) within bile ductular cells in ethionine-treated mice with NASH. Cells that coexpress epithelial and mesenchymal genes are generally considered to be undergoing epithelial-tomesenchymal (or mesenchymal-to-epithelial) transition.…”

Section: Hedgehog Activity and Nash Sv Fleig Et Almentioning

confidence: 84%

Hepatic accumulation of Hedgehog-reactive progenitors increases with severity of fatty liver damage in mice

Fleig

Choi

Yang

et al. 2007

Laboratory Investigation

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“…It is likely that MFG secretion is a highly derived form of apocrine secretion in which upregulation of milk fat secretion has required incorporation of novel membrane constituents (see Milk Fat Globule section, below). Unfortunately, little is known about the details of secretion in generalized apocrine glands or about the genes expressed and proteins synthesized (Oftedal, 2002b), although at least some types do not produce milkspecific proteins, such as b-casein (Gritli-Linde et al, 2007). From an evolutionary perspective, it would be very interesting to compare the array of genes expressed by developing and secreting apocrine glands with those expressed during mammary gland development, milk secretion, and mammary involution.…”

Section: The Evolution Of Mammary Secretionmentioning

confidence: 99%

The evolution of milk secretion and its ancient origins

Oftedal

2012

Animal

196

142

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Lactation represents an important element of the life history strategies of all mammals, whether monotreme, marsupial, or eutherian. Milk originated as a glandular skin secretion in synapsids (the lineage ancestral to mammals), perhaps as early as the Pennsylvanian period, that is, approximately 310 million years ago (mya). Early synapsids laid eggs with parchment-like shells intolerant of desiccation and apparently dependent on glandular skin secretions for moisture. Mammary glands probably evolved from apocrine-like glands that combined multiple modes of secretion and developed in association with hair follicles. Comparative analyses of the evolutionary origin of milk constituents support a scenario in which these secretions evolved into a nutrient-rich milk long before mammals arose. A variety of antimicrobial and secretory constituents were co-opted into novel roles related to nutrition of the young. Secretory calcium-binding phosphoproteins may originally have had a role in calcium delivery to eggs; however, by evolving into large, complex casein micelles, they took on an important role in transport of amino acids, calcium and phosphorus. Several proteins involved in immunity, including an ancestral butyrophilin and xanthine oxidoreductase, were incorporated into a novel membrane-bound lipid droplet (the milk fat globule) that became a primary mode of energy transfer. An ancestral c-lysozyme lost its lytic functions in favor of a role as a-lactalbumin, which modifies a galactosyltransferase to recognize glucose as an acceptor, leading to the synthesis of novel milk sugars, of which free oligosaccharides may have predated free lactose. An ancestral lipocalin and an ancestral whey acidic protein four-disulphide core protein apparently lost their original transport and antimicrobial functions when they became the whey proteins b-lactoglobulin and whey acidic protein, which with a-lactalbumin provide limiting sulfur amino acids to the young. By the late Triassic period (ca 210 mya), mammaliaforms (mammalian ancestors) were endothermic (requiring fluid to replace incubatory water losses of eggs), very small in size (making large eggs impossible), and had rapid growth and limited tooth replacement (indicating delayed onset of feeding and reliance on milk). Thus, milk had already supplanted egg yolk as the primary nutrient source, and by the Jurassic period (ca 170 mya) vitellogenin genes were being lost. All primary milk constituents evolved before the appearance of mammals, and some constituents may have origins that predate the split of the synapsids from sauropsids (the lineage leading to 'reptiles' and birds). Thus, the modern dairy industry is built upon a very old foundation, the cornerstones of which were laid even before dinosaurs ruled the earth in the Jurassic and Cretaceous periods.Keywords: evolution, lactation, milk composition, casein, milk fat globule ImplicationsLactation has an evolutionary origin and biological context within which its secretory processes and milk constituents evolved. This revi...

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Abnormal Hair Development and Apparent Follicular Transformation to Mammary Gland in the Absence of Hedgehog Signaling

Cited by 81 publications

References 34 publications

Involvement of Wnt, Eda and Shh at defined stages of sweat gland development

Involvement of Wnt, Eda and Shh at defined stages of sweat gland development

Hepatic accumulation of Hedgehog-reactive progenitors increases with severity of fatty liver damage in mice

The evolution of milk secretion and its ancient origins

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