Neurons form elaborate networks by guiding axons and dendrites to appropriate destinations. Neurites require information about the relative body axes during the initial projection from the cell body, and failure to receive or interpret those cues correctly can result in outgrowth errors. We identified a mutation in the Ig superfamily member syg-2 in a screen for animals with anterior/posterior (A/P) axon guidance defects. We found that syg-2 and its cognate Ig family member syg-1 appear to function in a linear genetic pathway to control the outgrowth of GABAergic axons. We determined that this pathway works in parallel to Wnt signaling. Specifically, mutations in syg-2 or syg-1 selectively affected the embryonically derived Dorsal D-type (DD) GABAergic neurons. We found no evidence that these mutations affected the Ventral D-type neurons (VD) that form later, during the first larval stage. In addition, mutations in syg-1 or syg-2 could result in the DD neurons forming multiple processes, becoming bipolar, rather than the expected pseudounipolar morphology. Given SYG-2's essential function in synaptogenesis of the hermaphrodite-specific neurons (HSNs), we also examined DD neuron synapses in syg-2 mutants. We found syg-2 mutants had a decreased number of synapses formed, but synaptic morphology was largely normal. These results provide further evidence that the GABAergic motorneurons use multiple guidance pathways during development.
An evaluation of transforming growth factor beta (TGFβ), hepatocyte growth factor (HGF), basic fibroblast growth factor (FGF-2), fibroblast growth factors receptor 1 (FGFR1) and Hox-positive cells in the human placenta, and their correlation with gestational time at delivery and pregnancy outcomes, may provide not only a better understanding of the role of Hox genes and growth factors in human development, but also may be of clinical importance in reproductive medicine. This study analyzed the immunohistochemical identification of TGFβ, HGF, FGF-2, FGFR1 and HoxB3 in placentas of various gestational ages. We found few (+) TGFβ, moderate (++) FGF-2 and numerous (+++) HGF and FGFR1 positive structures. Occasional (0/+) to numerous (+++) HoxB3-positive structures were detected in different types of placental cells specifically, cytotrophoblasts, syncytiotrophoblast, extravillous trophoblasts, and Höfbauer cells. Correlating the appearance of HoxB3 staining in placentas with neonatal parameters, we found a statistically significant negative correlation with ponderal index (r = -0.323, p = 0.018) and positive correlation with neonate body length (r = 0.541, p = 0.046). The number of HoxB3-positive cells did not correlate with growth factors and gestational age, but with neonatal anthropometrical parameters, indicating the role of HoxB3 not only in placental development, but also in the longitudinal growth of the fetus. TGFβ and FGF-2 did not play a significant role in the development of the placenta beyond 22nd week of pregnancy, while HGF and FGFR1 immunoreactive cells increased with advancing gestation, indicating increasingly evolving maturation (growth, proliferation) of the placenta, especially in the third trimester.
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