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Orchestrated proliferation, differentiation, and cell death contribute to the generation of the complex cytoarchitecture of the central nervous system, including that of the neuroretina. However, few studies have comprehensively compared the spatiotemporal patterns of these 3 processes, or their relative magnitudes. We performed a parallel study in embryonic chick and mouse retinas, focusing on the period during which the first neurons, the retinal ganglion cells (RGCs), are generated. The combination of in vivo BrdU incorporation, immunolabeling of retinal whole mounts for BrdU and for the neuronal markers Islet1/2 and β III-tubulin, and TUNEL allowed for precise cell scoring and determination the spatiotemporal patterns of cell proliferation, differentiation, and death. As predicted, proliferation preceded differentiation. Cell death and differentiation overlapped to a considerable extent, although the magnitude of cell death exceeded that of neuronal differentiation. Precise quantification of the population of recently born RGCs, identified by BrdU and β III-tubulin double labeling, combined with cell death inhibition using a pan-caspase inhibitor, revealed that apoptosis decreased this population by half shortly after birth. Taken together, our findings provide important insight into the relevance of cell death in neurogenesis.

Previous studies on double deficient mice for leukemia inhibitory factor (LIF) and insulin-like growth factor I (IGF-I) reported that they died of respiratory failure, with abnormal lung histology and altered expression of pulmonary markers. Here we analyzed prenatal Lif/Igf-I double mutant mouse embryos to characterize LIF and IGF-I cooperative roles in distal lung epithelium and vascular maturation. Lungs of IGF-I-deficient embryos displayed a higher proportion of type II pneumocytes, less differentiated type I pneumocytes, and failure in alveolar capillary remodeling compared to wild type and LIF-deficient mice. Lif/Igf-I double knockout lungs showed aggravated pulmonary hypoplasia, lower airway volume, increased proliferation, and elevated levels of ERK1/2 activation. In addition, their alveoli were collapsed and lined by type II cells. The differentiation of type I cells barely occurred and capillaries remained in the abundant mesenchyme. These results indicate that LIF collaborates with IGF-I in lung alveolar epithelium and vascular maturation.

cCdx-B (formerly cHox-cad 2) is a chick homeobox-containing gene related to the Drosophila caudal. Compared with other caudal homologues, its similarity is highest with the murine Cdx-4. In the present study, we characterize the localization of cCdx-B transcripts to the caudal region of the embryo by using reverse transcription-polymerase chain reaction (RT-PCR) and, in detail, by using in situ hybridization. Chick embryos from gastrulation to early organogenesis were hybridized with digoxigenin-labeled riboprobes, and the pattern of expression of cCdx-B mRNA was analyzed in wholemount embryos and in tissue sections. In the early gastrula, transcripts were localized in a gradient through the caudal half of the embryo, in the epiblast and the mesoderm cells, but not including Hensen's node. During neurulation, cCdx-B transcripts were found more rostrally, with high levels localized in Hensen's node and the posterior neural plate. Expression was also high in paraxial mesoderm, with a rostral limit in the most recently formed somite. There was no expression in definitive endoderm. During late neurulation and tail bud formation, cCdx-B mRNA expression regressed posteriorly and was finally confined to the tail bud region. This pattern of expression of cCdx-B, regulated in time and space, is different from that of the other known chick caudal homologue, cCdx-A. Both genes may play a coordinated role in the posterior axial patterning of the chick embryo, whereas cCdx-B may specify further the identity of the tail region.

Ectopic implantation of the embryo in the tube opposite to the ovary containing the corpus luteum constitutes evidence of peritoneal or uterine transmigration of the egg. The frequency of this phenomenon was reinvestigated utilizing histopathologic confirmation of the side of the corpus luteum. A tubal pregnancy contralateral to the ovulating ovary was found in 28% of 67 cases, indicating that either the oocyte, the zygote or the embryo had entered the tube in which implantation took place from a medial site such as the peritoneal or the uterine cavity rather than directly from the ovulating ovary. Assuming that once in the medial site there is equal chance of entering either tube, it follows that in 56% of tubal pregnancies the egg has entered the tube from a midline location. Attempts to recover the oocyte from the tubes in normal women were successful in fewer than 5% of cases contralateral to the corpus luteum. It is concluded that tubal pregnancy is associated with a significant increase in the occurrence of transmigration of the egg.