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Publication : Identification of the scaramanga gene implicates Neuregulin3 in mammary gland specification.

First Author  Howard B Year  2005
Journal  Genes Dev Volume  19
Issue  17 Pages  2078-90
PubMed ID  16140987 Mgi Jnum  J:100495
Mgi Id  MGI:3588629 Doi  10.1101/gad.338505
Citation  Howard B, et al. (2005) Identification of the scaramanga gene implicates Neuregulin3 in mammary gland specification. Genes Dev 19(17):2078-90
abstractText  The mouse scaramanga (ska) mutation impairs mammary gland development such that both abrogation and stimulation of gland formation occurs. We used positional cloning to narrow the interval containing scaramanga (ska) to a 75.6-kb interval containing the distal part of the Neuregulin3 (Nrg3) gene. Within this region the only sequence difference between ska and wild-type mice is in a microsatellite repeat within intron 7. This alteration correlates with variations in Nrg3 expression profiles both at the whole embryo level and locally in the presumptive mammary region in ska mice. Localized expression of Nrg3 and its receptor, Erbb4, in the presumptive mammary region around the future bud site prior to morphological appearance of buds and the expression of bud epithelial markers further support an inductive role. Finally, Neuregulin3 (Nrg3)-soaked beads can induce expression of the early bud marker Lef1 in mouse embryo explant cultures, and epithelial bud formation can be observed histologically, suggesting that initiation of mammary bud development occurs. Taken together, these results indicate that a Neuregulin signaling pathway is involved in specification of mammary gland morphogenesis and support the long-held view that mesenchymal signal(s) are responsible for mammary gland inductive/initiating events.
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