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During embryogenesis, primordial germ cells (PGCs) and somatic gonadal precursor cells (SGPs) migrate and coalesce to form the early gonad. A failure of the PGCs and SGPs to form a gonad with the proper architecture not only affects germ cell development, but can also lead to infertility. Therefore, it is critical to identify the molecular mechanisms that function within both the PGCs and SGPs to promote gonad morphogenesis. We have characterized the phenotypes of two genes, longitudinals lacking (lola) and ribbon (rib), that are required for the coalescence and compaction of the embryonic gonad in Drosophila melanogaster. rib and lola are expressed in the SGPs of the developing gonad, and genetic interaction analysis suggests these proteins cooperate to regulate gonad development. Both genes encode proteins with DNA binding motifs and a conserved protein-protein interaction domain, known as the Broad complex, Tramtrack, Bric-à-brac (BTB) domain. Through molecular modeling and yeast-two hybrid studies, we demonstrate that Rib and Lola homo- and heterodimerize via their BTB domains. In addition, analysis of the colocalization of Rib and Lola with marks of transcriptional activation and repression on polytene chromosomes reveals that Rib and Lola colocalize with both repressive and activating marks and with each other. While previous studies have identified Rib and Lola targets in other tissues, we find that Rib and Lola are likely to function via different downstream targets in the gonad. These results suggest that Rib and Lola act as dual-function transcription factors to cooperatively regulate embryonic gonad morphogenesis., Competing Interests: The authors have declared that no competing interests exist.

The free thyroxine (FT4) test of Clinical Assays, Corning Medical, and Damon Diagnostics were evaluated in 245 patients. Although all three assays generally correlated well with the clinical functional status, there were apparent discrepancies in the clinically euthyroid population. All patients with discordant values had either relatively high or low triiodothyronine (T3) uptakes. In these instances, the free-thyroxine index gave a more accurate assessment of the clinical thyroid status than did the FT4. In our opinion, these findings place a critical limitation on these assays as a replacement for the free-thyroxine index.

The free thyroxine index (FTI) and a free thyroxine (FT4) assay were compared with the thyrotropin-releasing hormone stimulation test in 98 consecutive patients to determine whether the FT4 assay is more sensitive than the FTI in screening patients for minimal hypothyroidism. FTI and FT4 values did not agree with the clinical evaluation in 20% (3/15) of the patients with a transitional thyroid-stimulating hormone (TSH) response (21 to 35 microU/ml) and in 64.3% (9/14) of the patients with an augmented TSH response (greater than 35 microU/ml). From these results we conclude that the FT4 assay is no more sensitive than the FTI in detection of such minimal thyroid dysfunction.