In humans, testis development depends on a regulated genetic hierarchy initiated 
by the Y-linked SRY gene. Failure of testicular determination results in the 
condition termed 46,XY gonadal dysgenesis (GD). Several components of the testis 
determining pathway have recently been identified though it has been difficult 
to articulate a cascade with the known elements of the system. It seems, 
however, that early gonadal development is the result of a network of 
interactions instead of the outcome of a linear cascade. Accumulating evidence 
shows that testis formation in man is sensitive to gene dosage. 
Haploinsufficiency of SF1, WT1 and SOX9 is responsible for 46,XY gonadal 
dysgenesis. Besides, data on SRY is consistent with possible dosage anomalies in 
certain cases of male to female sex reversal. 46,XY GD due to monosomy of distal 
9p and 10q might also be associated with an insufficient gene dosage effect. 
Duplications of the locus DSS can lead to a failure of testicular development 
and a duplication of the region containing SOX9 has been implicated in XX sex 
reversal. Transgenic studies in mouse have shown, however, that this mammal is 
less sensitive to gene dosage than man. Here, we will try to put in place the 
known pieces of the jigsaw puzzle that is sex determination in mammals, as far 
as current knowledge obtained from man and animal models allows. We are certain 
that from this attempt more questions than answers will arise.