Making embryos male

Dr. Blanche Capel and colleagues at Duke University Medical Center (NC) and Curis, Inc. (MA) have determined that a cell-signaling molecule called Desert Hedgehog, or DHH, is required for the differentiation of male-specific Leydig cells in the developing embryo. Fetal Leydig cells are the cells within the testis that produce testosterone during development, and thereby impart secondary male sex characteristics to the embryo, including the internal and external male genitalia.

This discovery posits DHH as the only known factor to induce fetal Leydig cell differentiation. DHH is one of three mammalian homologs of a protein called Hedgehog, which was originally identified in the Drosophila fruit fly, where it regulates body pattern formation. Although all three mammalian Hedgehog homologs have important signaling functions during development, this work by Dr. Capel and colleagues demonstrates a primary role for DHH in establishing secondary male sex characteristics.

To study the potential role of DHH in fetal Leydig cell differentiation, Dr. Capel and colleagues first examined the expression pattern of Dhh within developing mouse embryos. They found that DHH and its receptor, Patched 1, were specifically expressed in XY (male) embryos in a temporally and spatially restricted pattern that corresponds to the correct time and place for fetal Leydig cell differentiation. Encouraged by these findings, Dr. Capel and colleagues analyzed mice that were genetically engineered to lack DHH. In male DHH-deficient mice, the Leydig cell precursors appeared intact, but the mice mice display defects in the differentiation of the precursors into Leydig cells, thereby establishing an integral role of DHH in fetal Leydig cell differentiation.

Dr. Capel and colleagues did note, though, that although all fetal Leydig cells express the DHH receptor, Patched 1, not all Patched 1-expressing cells become fetal Leydig cells. This key observation points to the existenc

Contact: Heather Coselpie
Cold Spring Harbor Laboratory

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