Crosstalk between the p190-B RhoGAP and IGF signaling pathways is required for embryonic mammary bud development

Brandy M. Heckman, Geetika Chakravarty, Tracy Vargo-Gogola, Maria Gonzales-Rimbau, Darryl L. Hadsell, Adrian V. Lee, Jeffrey Settleman, Jeffrey M. Rosen

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

P190-B RhoGAP (p190-B, also known as ARHGAP5) has been shown to play an essential role in invasion of the terminal end buds (TEBs) into the surrounding fat pad during mammary gland ductal morphogenesis. Here we report that embryos with a homozygous p190-B gene deletion exhibit major defects in embryonic mammary bud development. Overall, p190-B-deficient buds were smaller in size, contained fewer cells, and displayed characteristics of impaired mesenchymal proliferation and differentiation. Consistent with the reported effects of p190-B deletion on IGF-1R signaling, IGF-1R-deficient embryos also displayed a similar small mammary bud phenotype. However, unlike the p190-B-deficient embryos, the IGF-1R-deficient embryos exhibited decreased epithelial proliferation and did not display mesenchymal defects. Because both IGF and p190-B signaling affect IRS-1/2, we examined IRS-1/2 double knockout embryonic mammary buds. These embryos displayed major defects similar to the p190-B-deficient embryos including smaller bud size. Importantly, like the p190-B-deficient buds, proliferation of the IRS-1/2-deficient mesenchyme was impaired. These results indicate that IGF signaling through p190-B and IRS proteins is critical for mammary bud formation and ensuing epithelial-mesenchymal interactions necessary to sustain mammary bud morphogenesis.

Original languageEnglish (US)
Pages (from-to)137-149
Number of pages13
JournalDevelopmental Biology
Volume309
Issue number1
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

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Breast
Embryonic Structures
Morphogenesis
Gene Deletion
Mesoderm
Human Mammary Glands
Adipose Tissue
Phenotype

Keywords

  • ARHGAP5
  • Epithelial-mesenchymal
  • IGF-1R
  • IRS-1
  • IRS-2
  • Mammary bud
  • p190-B

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Crosstalk between the p190-B RhoGAP and IGF signaling pathways is required for embryonic mammary bud development. / Heckman, Brandy M.; Chakravarty, Geetika; Vargo-Gogola, Tracy; Gonzales-Rimbau, Maria; Hadsell, Darryl L.; Lee, Adrian V.; Settleman, Jeffrey; Rosen, Jeffrey M.

In: Developmental Biology, Vol. 309, No. 1, 01.09.2007, p. 137-149.

Research output: Contribution to journalArticle

Heckman, BM, Chakravarty, G, Vargo-Gogola, T, Gonzales-Rimbau, M, Hadsell, DL, Lee, AV, Settleman, J & Rosen, JM 2007, 'Crosstalk between the p190-B RhoGAP and IGF signaling pathways is required for embryonic mammary bud development', Developmental Biology, vol. 309, no. 1, pp. 137-149. https://doi.org/10.1016/j.ydbio.2007.07.002
Heckman, Brandy M. ; Chakravarty, Geetika ; Vargo-Gogola, Tracy ; Gonzales-Rimbau, Maria ; Hadsell, Darryl L. ; Lee, Adrian V. ; Settleman, Jeffrey ; Rosen, Jeffrey M. / Crosstalk between the p190-B RhoGAP and IGF signaling pathways is required for embryonic mammary bud development. In: Developmental Biology. 2007 ; Vol. 309, No. 1. pp. 137-149.
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