Development of the vertebrate gut is controlled by paracrine crosstalk between the endodermal epithelium and the associated splanchnic mesoderm. In the adult, the same types of signals control epithelial proliferation and survival, which account for the importance of the stroma in colon carcinoma progression. Here, we show that targeting murine Foxf1 and Foxf2, encoding forkhead transcription factors, has pleiotropic effects on intestinal paracrine signaling. Inactivation of both Foxf2 alleles, or one allele each of Foxf1 and Foxf2, cause a range of defects, including megacolon, colorectal muscle hypoplasia and agangliosis. Foxf expression in the splanchnic mesoderm is activated by Indian and sonic hedgehog secreted by the epithelium. In Foxf mutants, mesenchymal expression of Bmp4 is reduced, whereas Wnt5a expression is increased. Activation of the canonical Wnt pathwaywith nuclear localization of ␤-catenin in epithelial cells -is associated with over-proliferation and resistance to apoptosis. Extracellular matrix, particularly collagens, is severely reduced in Foxf mutant intestine, which causes epithelial depolarization and tissue disintegration. Thus, Foxf proteins are mesenchymal factors that control epithelial proliferation and survival, and link hedgehog to Bmp and Wnt signaling.

The dysgenetic lens (dyl) mouse mutant has mutations in Foxe3, which inactivate DNA binding by the encoded forkhead transcription factor. Here we confirm, by targeted inactivation, that Foxe3 mutations are responsible for the dyl phenotype, which include loss of lens epithelium; a small, cataractic lens; and failure of the lens to detach from the surface ectoderm. In contrast to a recent report of targeted Foxe3, we found no phenotypic difference between dyl and Foxe3(-/-) mutants when congenic strains were compared, and thus nothing that argues against Foxe3(dyl) being a null allele. In addition to the lens, most tissues of the anterior segment-iris, cornea, ciliary body and trabecular meshwork-are malformed or show differentiation defects. Many of these abnormalities, such as irido-corneal and irido-lenticular adherences, are present in a less severe form in mice heterozygous for the Foxe3 mutation, in spite of these having an intact lens epithelium. Early Foxe3 expression is highly sensitive to a halved Pax6 gene dosage and there is a striking phenotypic similarity between Pax6 and Foxe3 mutants. We therefore propose that many of the ocular malformations associated with Pax6 haploinsufficiency are consequences of a reduced expression of Foxe3.

The phenomenon of adult neurogenesis has been demonstrated in most mammals including humans. At least two regions of the adult brain maintain stem cells throughout life; the subgranular zone (SGZ) of the hippocampal dentate gyrus, and the subventricular zone (SVZ) of the lateral ventricle wall. Both regions continuously produce neurons that mature and become integrated into functional networks that are involved in learning and memory and odor discrimination, respectively. Apart from these well-studied regions neurogenesis has been reported in a number of other brain regions, such as amygdala and cortex. However, these studies have been contested and there is currently no well-postulated function for non-SVZ/SGZ neurogenesis. The studies of the regional localization of neurogenesis in the brain have been made possible due to several methods for detecting adult neurogenesis including; bromodeoxyuridine labeling (BrdU) together with markers of mature neurons, genetic labeling, by mouse transgenesis, or with the use of viral vectors. These techniques are already put to creative use and will be essential for the discovery of the nature of the adult neural stem cells. In this mini-review, we will discuss the localization of neural stem/progenitor cells in the brain and their implications as well as discussing the pro's and con's of stem cell labeling techniques.

Proper inactivation of FoxE3 expression at the lens equator is important for many aspects of fiber differentiation, and persistent expression leads to a partial epithelialization of fiber cells, with severe consequences for lens function.

Forkhead transcription factors are important regulators of animal development. Here, we describe the embryonic expression pattern for one of the novel forkhead genes that were discovered as a result of the mouse and human genome projects. It is most closely related to FoxJ2 and has been assigned the name