Further Development 18.1: Hox Makes Cells Competent to Express Lim and Make a Kidney

Intermediate and Lateral Plate Mesoderm: Heart, Blood, and Kidneys

Lim1 plays several roles in the formation of the mouse kidney. Early in development it is needed for con-verting the intermediate mesenchyme into the nephric duct (Tsang et al. 2000), and later it is required for the formation of the ureteric bud and the nephrons that form from mesonephric and metanephric mesenchyme (Shawlot and Behringer 1995; Karavanov et al. 1998; Kobayashi et al. 2005).

The anterior border of the Lim1- and Pax2-expressing cells appears to be established by the cells above a certain region losing their competence to respond to activin, a TGF-β superfamily paracrine factor secreted by the neural tube. This competence to respond to activin is established by the transcription factor Hoxb4, which is not expressed in the anteriormost region of the intermediate mesoderm. The anterior boundary of Hoxb4 expression is established by a retinoic acid gradient; adding activin locally will overcome this gradient and allow the kidney to extend anteriorly (Barak et al. 2005; Preger-Ben Noon et al. 2009).

Literature Cited

Barak, H., L. Rosenfelder, T. M. Schultheiss and R. Reshef. 2005. Cell fate specification along the anterior-posterior axis of the intermediate mesoderm. Dev. Dyn. 232: 901–914. 
PubMed Link

Karavanov, A. A., I. Karavanova, A. Perantoni and I. B. Dawid. 1998. Expression pattern of the rat Lim-1 homeobox gene suggests a dual role during kidney development. Int. J. Dev. Biol. 42: 61–66.
PubMed Link

Kobayashi, A., K.-M. Kwan, T. J. Carroll, A. P. McMahon, C. L. Mendelsohn and R. R. Behringer. 2005. Dis-tinct and sequential tissue-specific activities of the LIM-class homeobox gene Lim1 for tub-ular morphogenesis during kidney development. Development 132: 2809–2823. 
PubMed Link

Preger-Ben Noon, E., H. Barak, N. Guttmann-Raviv and R. Reshef. 2009. Interplay between activin and Hox genes determines the formation of the kidney morphogenetic field. Development 136: 1995–2004.
PubMed Link

Shawlot, W. and R. R. Behringer. 1995. Requirement for Lim1 in head-organizer func-tion. Nature 374: 425–430.
PubMed Link

Tsang, T. E., W. Shawlot, S. J. Kinder, A. Kobayashi, K. M. Kwan, K. Schughart, A. Kania, T. M. Jessell, R. R. Behringer and P. P. Tam. 2000. Lim1 activity is required for intermediate mesoderm differentiation in the mouse embryo. Dev. Biol. 223: 77–90.
PubMed Link

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