Regulation of BMP7 expression during kidney development

Robert E. Godin, Norma T. Takaesu, Elizabeth J. Robertson, Andrew T. Dudley

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

Members of the Bone Morphogenetic Protein (BMP) family exhibit overlapping and dynamic expression patterns throughout embryogenesis. However, little is known about the upstream regulators of these important signaling molecules. There is some evidence that BMP signaling may be autoregulative as demonstrated for BMP4 during tooth development. Analysis of BMP7 expression during kidney development, in conjunction with studies analyzing the effect of recombinant BMP7 on isolated kidney mesenchyme, suggest that a similar mechanism may operate for BMP7. We have generated a β-gal-expressing reporter allele at the BMP7 locus to closely monitor expression of BMP7 during embryonic kidney development. In contrast to other studies, our analysis of BMP7/lacZ homozygous mutant embryos, shows that BMP7 expression is not subject to autoregulation in any tissue. In addition, we have used this reporter allele to analyze the expression of BMP7 in response to several known survival factors (EGF, bFGF) and inducers of metanephric mesenchyme, including the ureteric bud, spinal cord and LiCl. These studies show that treatment of isolated mesenchyme with EGF or bFGF allows survival of the mesenchyme but neither factor is sufficient to maintain BMP7 expression in this population of cells. Rather, BMP7 expression in the mesenchyme is contingent on an inductive signal. Thus, the reporter allele provides a convenient marker for the induced mesenchyme. Interestingly LiCl has been shown to activate the Wnt signaling pathway, suggesting that BMP7 expression in the mesenchyme is regulated by a Wnt signal. Treatment of whole kidneys with sodium chlorate to disrupt proteoglycan synthesis results in the loss of BMP7 expression in the mesenchyme whereas expression in the epithelial components of the kidney are unaffected. Heterologous recombinations of ureteric bud with either limb or lung mesenchyme demonstrate that expression of BMP7 is maintained in this epithelial structure. Taken together, these data indicate that BMP7 expression in the epithelial components of the kidney is not dependent on cell-cell or cell-ECM interactions with the metanephric mesenchyme. By contrast, BMP7 expression in the metanephric mesenchyme is dependent on proteoglycans and possibly Wnt signaling.

Original languageEnglish (US)
Pages (from-to)3473-3482
Number of pages10
JournalDevelopment
Volume125
Issue number17
StatePublished - Sep 1 1998

Fingerprint

Mesoderm
Kidney
Bone Morphogenetic Proteins
Alleles
Proteoglycans
Epidermal Growth Factor
Embryonic Development
Wnt Signaling Pathway
Cell Communication
Genetic Recombination
Spinal Cord
Tooth
Homeostasis
Embryonic Structures
Extremities
Lung

Keywords

  • BMPs
  • Cell signaling
  • Kidney
  • Mouse

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Godin, R. E., Takaesu, N. T., Robertson, E. J., & Dudley, A. T. (1998). Regulation of BMP7 expression during kidney development. Development, 125(17), 3473-3482.

Regulation of BMP7 expression during kidney development. / Godin, Robert E.; Takaesu, Norma T.; Robertson, Elizabeth J.; Dudley, Andrew T.

In: Development, Vol. 125, No. 17, 01.09.1998, p. 3473-3482.

Research output: Contribution to journalArticle

Godin, RE, Takaesu, NT, Robertson, EJ & Dudley, AT 1998, 'Regulation of BMP7 expression during kidney development', Development, vol. 125, no. 17, pp. 3473-3482.
Godin RE, Takaesu NT, Robertson EJ, Dudley AT. Regulation of BMP7 expression during kidney development. Development. 1998 Sep 1;125(17):3473-3482.
Godin, Robert E. ; Takaesu, Norma T. ; Robertson, Elizabeth J. ; Dudley, Andrew T. / Regulation of BMP7 expression during kidney development. In: Development. 1998 ; Vol. 125, No. 17. pp. 3473-3482.
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