TY - JOUR
T1 - Synergism between Pax-8 and lim-1 in embryonic kidney development
AU - Carroll, Thomas J.
AU - Vize, Peter D.
N1 - Funding Information:
The authors thank Paul Krieg and Ondine Cleaver for comments on the manuscript, Gary Freeman and Antone Jacobson for useful input, and Igor Dawid and Greg Dressler for reagents. This research was supported by NSF Grant IBN 9630621 and the Center for Developmental Biology.
PY - 1999/10/1
Y1 - 1999/10/1
N2 - Pax genes encode a family of highly conserved DNA-binding transcription factors. These proteins play key roles in regulating a number of vertebrate and invertebrate developmental processes. Mutations in Pax-6 result in eye defects in flies, mice, and humans, and ectopic expression of this gene can trigger the development of ectopic compound eyes in flies. Likewise, mutation of other Pax genes in vertebrates results in the failure of specific differentiation programs - Pax-1 causes skeletal defects; Pax-2, kidney defects; Pax-3 or Pax-7, neural crest defects; Pax-4, pancreatic β-cell defects; Pax-5, B-cell defects; Pax-8, thyroid defects; and Pax-9, tooth defects. Although this class of genes is obviously required for the normal differentiation of a number of distinct organ systems, they have not previously been demonstrated to be capable of directing the embryonic development of organs in vertebrates. In this report, it is demonstrated that Pax-8 plays such a role in the establishment of the Xenopus embryonic kidney, the pronephros. However, in order to efficiently direct cells to form pronephric kidneys, XPax-8 requires cofactors, one of which may be the homeobox transcription factor Xlim-1. These two genes are initially expressed in overlapping domains in late gastrulae, and cells expressing both genes will go on to form the kidney. Ectopic expression of either gene alone has a moderate effect on pronephric patterning, while coexpression of XPax-8 plus Xlim-1 results in the development of embryonic kidneys of up to five times normal complexity and also leads to the development of ectopic pronephric tubules. This effect was synergistic rather than additive. XPax-2 can also synergize with Xlim-1, but the expression profile of this gene indicates that it normally functions later in pronephric development than does XPax-8. Together these data indicate that the interaction between XPax-8 and Xlim-1 is a key early step in the establishment of the pronephric primordium.
AB - Pax genes encode a family of highly conserved DNA-binding transcription factors. These proteins play key roles in regulating a number of vertebrate and invertebrate developmental processes. Mutations in Pax-6 result in eye defects in flies, mice, and humans, and ectopic expression of this gene can trigger the development of ectopic compound eyes in flies. Likewise, mutation of other Pax genes in vertebrates results in the failure of specific differentiation programs - Pax-1 causes skeletal defects; Pax-2, kidney defects; Pax-3 or Pax-7, neural crest defects; Pax-4, pancreatic β-cell defects; Pax-5, B-cell defects; Pax-8, thyroid defects; and Pax-9, tooth defects. Although this class of genes is obviously required for the normal differentiation of a number of distinct organ systems, they have not previously been demonstrated to be capable of directing the embryonic development of organs in vertebrates. In this report, it is demonstrated that Pax-8 plays such a role in the establishment of the Xenopus embryonic kidney, the pronephros. However, in order to efficiently direct cells to form pronephric kidneys, XPax-8 requires cofactors, one of which may be the homeobox transcription factor Xlim-1. These two genes are initially expressed in overlapping domains in late gastrulae, and cells expressing both genes will go on to form the kidney. Ectopic expression of either gene alone has a moderate effect on pronephric patterning, while coexpression of XPax-8 plus Xlim-1 results in the development of embryonic kidneys of up to five times normal complexity and also leads to the development of ectopic pronephric tubules. This effect was synergistic rather than additive. XPax-2 can also synergize with Xlim-1, but the expression profile of this gene indicates that it normally functions later in pronephric development than does XPax-8. Together these data indicate that the interaction between XPax-8 and Xlim-1 is a key early step in the establishment of the pronephric primordium.
KW - Nephric duct
KW - Nephric tubule
KW - Nephron
KW - Pronephric
KW - Pronephros
KW - Xenopus
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U2 - 10.1006/dbio.1999.9414
DO - 10.1006/dbio.1999.9414
M3 - Article
C2 - 10491256
AN - SCOPUS:0033215449
SN - 0012-1606
VL - 214
SP - 46
EP - 59
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -