Analysis of Biological Development (K. Kalthoff)

Updates to Topic 26: Sex Determination


Answers to Questions in Text

Primary Site of Tdy Action

  1. How could the investigators know whether a given chimeric mouse had XY cells from the GPI-A strain, or the GPI-B strain, or both? Answer: The two mouse strains had morphologically distinct Y chromosomes.
  2. How should the result of the electrophoretic test shown in the bottom part of Fig. 26.8 look if the XX cells had been contributed by the GPI-B strain? Answer: The XX-GPI-B row would have been at the bottom, due to the greater electrophoretic mobilities of this enzyme isoform. Again, this row should have had no stained band in the Sertoli column.
  3. What would you have concluded from a single test result as shown in Fig. 26.8 if in the XX-GPI-A row there had been no stained band in the middle column (Leydig cells)? Answer: That in this particular individual virtually all Leydig cells had been contributed by the XY-GPI-B cells. Such a result may in fact have been found. However, the conclusion that Tdy action is required in Leydig cells would have been justified only if this result had been observed consistently in a large number of chimeras.

XX Mice Made Transgenic for Sry+

  1. What was the purpose of testing the potentially transgenic mice for the presence of the Zfy+ gene? Answer: The investigators wanted to eliminate sex-reversed males, which would be karyotyped as XX but carry an undetected Y chromosome fragment as a result of meiotic crossover (see Figs. 26. 9 and 26.10).
  2. How do you interpret the fact that the single adult male described here was defective in spermatogenesis and infertile? Answer: In addition to Sry+, there are a few other Y-linked genes, including genes required for spermatogenesis.The transgenic male did not have these genes.
  3. How do you interpret the fact that only 3 out of 11 XX individuals with an Sry+ transgene developed as gonadal males? Why not all of them? Answer: There are several possible explanations. First, the 14-kb DNA fragment used in the experiment may not have included all regulatory regions of the Sry+ gene, leaving Sry+ activity marginal or unstable. Second, the Sry+ transgene may have been poorly expressed, as the expression of transgenes in mice depends on their chromosomal location (see Section 15.XX). Third, the Sry+ transgene may have been present only in some tissues, but not in the testes, of some of the transgenic mice. Finally, the principle of synergistic mechanisms may apply. There may be one or more Y-linked genes that act synergistically with Sry+, so that Sry+ by itself functions only sporadically. Indeed, sex-reversed human males often show irregularities in their reproductive organs other than defective spermatogenesis.

Comments

Clarifications and Corrections

New Review Articles

Hawley R.S. (2203) The human Y chromosome: Rumors of its death have been greatly exaggerated. Cell 113: 825-828

Park Y. and Kuroda M. (2001) Epigenetic aspects of X chromosome dosage compensation. Science 293: 1083-1085

Sarre S.D., Georges A. and Quinn A. (2004) The ends of a continuum: Genetic and temperature-dependent sex determination in reptiles. BioEssays 26: 639-645

Sanchez L. and Guerrero I. (2001) The development of the Drosophila genital disc. Bioessays 23: 698-707

Vincent S, Perkins LA, and Perrimon N. (2001) Doublesex surprises. Cell 106: 399-402

New Research Articles

Keisman E.L. and Baker B.S. (2001) The Drosophila sex determination hierarchy modulates wingless and decapentaplegic signaling to deploy dachshund sex-specifically in the genital imaginal disc. Development 128: 16431656.

Sanchez L., Gorfinkiel N., and Guerrero I. (2001) Sex determination genes control the development of the Drosophila genital disc, modulating the response to Hedgehog, Wingless and Decapentaplegic signals. Development 128: 1033-1043

In both sexes, the Drosophila genital disc contains the female and male genital primordia. The sex determination gene doublesex+ controls which of these primordia will develop and which will be repressed. In females, the presence of Doublesex(F) product results in the development of the female genital primordium and repression of the male primordium. In males, the presence of Doublesex(M) product results in the development and repression of the male and female genital primordia, respectively. These two studies show that the gene dachshund+ (dac+) is differentially expressed in the male and female genital discs, and plays sex-specific roles in the development of the genitalia. Ectopic gene expression in labeled clones reveals that the sex determination hierarchy mediates this sex-specific expression of dac through the pattern formation genes wingless+ (wg+) and decapentaplegic+ (dpp+). The sex determination pathway acts cell-autonomously to determine whether dac is activated by wg signaling, as in females, or by dpp signaling, as in males.


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