Regulation of outgrowth and apoptosis for the terminal appendage: External genitalia: Development by concerted actions of BMP signaling

Kentaro Suzuki, Daniel Bachiller, Yi Ping P. Chen, Mami Kamikawa, Hidenao Ogi, Ryama Haraguchi, Yukiko Ogino, Yasuhiro Minami, Yuji Mishina, Kyung Ahn, E. Bryan Crenshaw, Gen Yamada

Research output: Contribution to journalReview article

96 Citations (Scopus)

Abstract

Extra-corporal fertilization depends on the formation of copulatory organs: the external genitalia. Coordinated growth and differentiation of the genital tubercle (GT), an embryonic anlage of external genitalia, generates a proximodistally elongated structure suitable for copulation, erection, uresis and ejaculation. Despite recent progress in molecular embryology, few attempts have been made to elucidate the molecular developmental processes of external genitalia formation. Bone morphogenetic protein genes (Bmp genes) and their antagonists were spatiotemporally expressed during GT development. Exogenously applied BMP increased apoptosis of GT and inhibited its outgrowth. It has been shown that the distal urethral epithelium (DUE), distal epithelia marked by the Fgf8 expression, may control the initial GT outgrowth. Exogenously applied BMP4 downregulated the expression of Fgf8 and Wnt5a, concomitant with increased apoptosis and decreased cell proliferation of the GT mesenchyme. Furthermore, noggin mutants and Bmpr1a conditional mutant mice displayed hypoplasia and hyperplasia of the external genitalia respectively. noggin mutant mice exhibited downregulation of Wnt5a and Fgf8 expression with decreased cell proliferation. Consistent with such findings, Wnt5a mutant mice displayed GT agenesis with decreased cell proliferation. By contrast, Bmpr1a mutant mice displayed decreased apoptosis and augmented Fgf8 expression in the DUE associated with GT hyperplasia. These results suggest that some of the Bmp genes could negatively affect proximodistally oriented outgrowth of GT with regulatory functions on cell proliferation and apoptosis. The DUE region can be marked only until 14.0 dpc (days post coitum) in mouse development, while GT outgrowth continues thereafter. Possible signaling crosstalk among the whole distal GT regions were also investigated.

Original languageEnglish
Pages (from-to)6209-6220
Number of pages12
JournalDevelopment
Volume130
Issue number25
DOIs
Publication statusPublished - Dec 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

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    Suzuki, K., Bachiller, D., Chen, Y. P. P., Kamikawa, M., Ogi, H., Haraguchi, R., Ogino, Y., Minami, Y., Mishina, Y., Ahn, K., Crenshaw, E. B., & Yamada, G. (2003). Regulation of outgrowth and apoptosis for the terminal appendage: External genitalia: Development by concerted actions of BMP signaling. Development, 130(25), 6209-6220. https://doi.org/10.1242/dev.00846