Developmental stalling and organ-autonomous regulation of morphogenesis.

Timing of organ development during embryogenesis is coordinated such that at birth, organ and fetal size and maturity are appropriately proportioned. The extent to which local developmental timers are integrated with each other and with the signaling interactions that regulate morphogenesis to achieve this end is not understood. Using the absolute requirement for a signaling pathway activity (bone morphogenetic protein, BMP) during a critical stage of tooth development, we show that suboptimal levels of BMP signaling do not lead to abnormal morphogenesis, as suggested by mutants affecting BMP signaling, but to a 24-h stalling of the intrinsic developmental clock of the tooth. During this time, BMP levels accumulate to reach critical levels whereupon tooth development restarts, accelerates to catch up with development of the rest of the embryo and completes normal morphogenesis. This suggests that individual organs can autonomously control their developmental timing to adjust their stage of development to that of other organs. We also find that although BMP signaling is critical for the bud-to-cap transition in all teeth, levels of BMP signaling are regulated differently in multicusped teeth. We identify an interaction between two homeodomain transcription factors, Barx1 and Msx1, which is responsible for setting critical levels of BMP activity in multicusped teeth and provides evidence that correlates the levels of Barx1 transcriptional activity with cuspal complexity. This study highlights the importance of absolute levels of signaling activity for development and illustrates remarkable self-regulation in organogenesis that ensures coordination of developmental processes such that timing is subordinate to developmental structure.

1,3-dinitrobenzene toxicity in the least shrew, Cryptotis parva.

Shrews are abundant in most areas of toxic chemical contamination and bioaccumulate pollutants at much higher rates than sympatric rodent species. As a part of studies to provide information concerning the toxicity of 1,3-dinitrobenzene (DNB) in least shrews (Cryptotis parva), groups of 10 females and 10 males received DNB at 0 (control), 0.7, 2.9, 11.6, and 46.3 microl/L (equivalent mean daily dosage of 0, 0.26, 1.06, 4.26, and 17.0 mg/kg body wt in each sex) in their diet for 14 d. Leukocytosis present at the 0.26 mg/kg body weight/d dosage established the lowest-observed-adverse effect level (LOAEL). Adrenal enlargement was noted at the 1.06 mg/kg body weight/d level. Splenic enlargement and reductions in hematocrit and hemoglobin values occurred at the 4.26 mg/kg body weight/d treatment. Enlargements in the liver and heart and reductions in brown fat weight, granulocyte numbers, and alanine aminotransferase levels were present at high dose levels. Histopathologic examinations showed Kupffer's cell hemosiderosis and suggested testicular damage at the two highest tested doses but failed to confirm brain lesions. Least shrews do not follow standard scaling estimates for lifespan or metabolic rates. The LOAEL calculated from the standard terrestrial screening benchmark equation was higher than our findings, suggesting that these estimates must be viewed with caution.

Novelties of conception in insectivorous mammals (Lipotyphla), particularly shrews.

In the order Lipotyphla (Insectivora), certain reproductive features differ quite distinctly from the eutherian norms, and are of interest with regard to the evolution of mammalian gamete function and perhaps for questions of lipotyphlan phylogeny. As seen in one or more members of five lipotyphlan families (shrews, moles, hedgehogs, golden moles, tenrecs), these features can involve the configuration of the male tract including the penis, the morphology of the sperm head, the anatomy of the oviduct and the patterns of sperm transport within it, the character of the cumulus oophorus, and the way in which fertilising spermatozoa interact with the eggs. However, the picture is by no means uniform within the order. Reproductive idiosyncrasies occur variously in the different lipotyphlan families, and appear consistently and strikingly in shrews--the group studied most extensively. Compared to the patterns in most Eutheria, the most interesting anomalies in soricids include (a) the regulation of sperm transport to the site of fertilisation by oviduct crypts, whose arrangement can vary even according to species, (b) a circumscribed matrix-free cumulus oophorus that appears essential for fertilisation as the inducer of the acrosome reaction, (c) barbs on the acrosome-reacted sperm head by which it may attach to the zona pellucida. With regard to the bearing such reproductive traits might have on lipotyphlan systematics, the African mouse shrew (Myosorex varius) displays a mix of traits that characterize either crocidurine or soricine shrews, consistent with the proposal that it belongs in a more primitive tribe, Myosoricinae, or subfamily, the Crocidosoricinae, from which the crocidurine and soricine lines probably evolved. Moreover, although elephant shrews are assigned now to a separate order (Macroscelidea), they display several of the unusual reproductive features seen in lipotyphlans, particularly in chrysochlorids and tenrecs. On the other hand, if used as a phylogenetic yardstick, none of the reproductive features described serves to define the Lipotyphla as classically constituted within one order, nor necessarily all the relationships suggested by recent sequencing studies of nuclear and mitochondrial genes.