Highlights in DD


  • Julie C. Kiefer

“Highlights” calls attention to exciting advances in developmental biology that have recently been reported in Developmental Dynamics. Development is a broad field encompassing many important areas. To reflect this fact, the section will spotlight significant discoveries that occur across the entire spectrum of developmental events and problems: from new experimental approaches, to novel interpretations of results, to noteworthy findings utilizing different developmental organisms.

Out on a limb (Dev Dyn236:2721–2730) When Ayala-Camargo et al. saw that their flies had extra legs, and antenna with duplicated segments, they knew they had uncovered something remarkable. The Drosophila had clones devoid of stat92E, a JAK/STAT pathway effector that, until now, had been firmly designated as a regulator of growth and proliferation. Here, the authors show that the Jak kinase ligand, Upd, is expressed in two domains in leg and antenna imaginal disks that are mutually exclusive of Wingless (Wg) and Decapentaplegic (Dpp), suggesting a role in patterning. Indeed, JAK/STAT represses expression of the two signaling molecules, which specify the proximal–distal (p–d) axis. Loss of stat92E triggers ectopic wg, and less consistently dpp, as well as downstream p–d patterning genes. Wg and Dpp, in turn, repress Upd. When expression of either wg or dpp is knocked down, upd's two expression domains converge. From these observations stems the model that leg and antenna p–d axes are patterned by mutual repression between JAK/STAT and Wg and to a lesser extent, JAK/STAT and Dpp. Given that Drosophila molecular mechanisms are often conserved, examining JAK/STAT's role in mammalian limb patterning would likely be worthwhile.

Niche machinery (Dev Dyn236:2836–2843) Just as a 4-wheel drive is a car designed to handle specialized conditions, niche TBP-associated factors (TAFs) mediate transcription of cell-type specific genes. TFIID, an integral part of the transcription initiation complex, is composed of TBP and several TAF subunits. Here, Metcalf and Wassarman test the hypothesis that the five Drosophila testis-specific TAFs (tTAFs) are subunits of a tTFIID. They find that general TAFs 1, 4, 5, and 9 are expressed in proliferating spermatogonia. In premeiotic spermatocytes, when tTAFs initiate expression, the general TAFs either cease expression or fail to colocalize with tTAFs. The exception is TAF1, which colocalizes with the tTAF Meiosis I arrest (Mia) in the premeiotic spermatocyte nucleolus. Although an isoform of TAF1 is testis-enriched, it does not behave like a tTAF. After meiosis I prophase, Mia and TAF1 fail to colocalize. Furthermore, in single tTAF mutants, other tTAFs are largely unperturbed while TAF1 becomes excluded from the nucleolus. These observations suggest that TFIID is replaced by tTFIID in spermatocytes and that association of TAF1 is both dependent on tTAFs and is developmentally regulated. Future studies will elucidate the role of TAF1 in the sperm-specific transcription machine.

Modifying expectations (Dev Dyn236:2943–2951) The discovery of Alagille syndrome's etiology is a satisfying example of developmental and clinical biology coming together. Mice double heterozygous for Notch2 and Jag1 model the disease, prompting clinicians to determine that some of the disease's variable phenotypes result from modifier effects of NOTCH2 on JAG1 haploinsufficiency. With similar promise, Loomes et al. reveal genetic interactions between Notch1 receptor and Delta-like 3 (Dll3), a putative ligand. While single heterozygotes for Notch1 and Dll3 appear wild-type, double heterozygotes exhibit vertebral and rib anomalies that model human congenital scoliosis, a spinal disorder with unknown etiology. Additionally, double hets display statistically significant maxillary hard palate lengthening and reduction of mandibular height, the first report of craniofacial defects in Dll3 mutants. Backing up these observations, Dll3 and Notch1 are expressed in developing craniofacial structures. How might genetic interactions between Dll3 and Notch1 affect craniofacial development? Microarray analysis was used to identify common target genes. Of note are homeobox gene Barx1 and the transcription factor Id4, whose expression patterns suggest roles in craniofacial development. Outcomes of this study may prove useful in identifying causes of vertebral and craniofacial birth defects.