Hox genes code for transcription factors that play a major role in the development of all animal phyla. In invertebrates these genes usually occur as tightly linked cluster, with a few exceptions where the clusters have been dissolved. Only in vertebrates multiple clusters have been demonstrated which arose by duplication from a single ancestral cluster. This history of Hox cluster duplications, in particular during the early elaboration of the vertebrate body plan, is still poorly understood. In this paper we report the results of a PCR survey on genomic DNA of the pacific hagfish Eptatretus stoutii. Hagfishes are one of two clades of recent jawless fishes that are an offshoot of the early radiation of jawless vertebrates. Our data provide evidence for at least 33 distinct Hox genes in the hagfish genome, which is most compatible with the hypothesis of multiple Hox clusters. The largest number, seven, of distinct homeobox fragments could be assigned to paralog group 9, which could imply that the hagfish has more than four clusters. Quartet mapping reveals that within each paralog group the hagfish sequences are statistically more closely related to gnathostome Hox genes than with either amphioxus or lamprey genes. These results support two assumptions about the history of Hox genes: (1) The association of hagfish homeobox sequences with gnathostome sequences suggests that at least one Hox cluster duplication event happened in the stem of vertebrates, i.e., prior to the most recent common ancestor of jawed and jawless vertebrates. (2) The high number of paralog group 9 sequences in hagfish and the phylogenetic position of hagfish suggests that the hagfish lineage underwent additional independent Hox cluster/-gene duplication events.

All multicellular organisms constantly need to replace aged or damaged cells. This vital task of tissue homeostasis is fulfilled by stem cells. The balance between self-renewal and differentiation of the stem cell is crucial for this task and tightly regulated by a signaling microenvironment termed the niche. A widely used model for studying stem cell niche biology is the Drosophila testis, where two stem cell populations, the germline stem cells (GSCs) and the somatic cyst stem cells (CySCs), reside in a niche located at the apical tip. A lot is known about the signals regulating GSC maintenance in the testicular niche. It is, however, unknown how the spatial regulation of these signals defines the range of the niche. Here I show, that Bone Morphogenetic Protein (BMP) signaling is specifically activated at the interface of niche and stem cells. This local activation is achieved by coupling the transport of adhesion and signaling molecules in the niche cells and directing their transport to contact sites of niche and stem cells. Localized niche signaling at junctions underlies the so called stem-cell-niche synapse hypothesis proposed for the mammalian hematopoietic stem cell niche. I have shown that disrupting the localized transport causes premature differentiation and stem cell loss. BMP signaling between niche and GSCs therefore provides the first description of a stem-cell-niche synapse and will yield valuable insights into mammalian stem cell biology. The CySCs reside in the niche of the testis together with the GSCs. To understand how the niche maintains both stem cell types in a concerted way, it is essential to know the pathways regulating both stem cell types. Here I show that Hedgehog (Hh) signaling is a key stem cell factor of CySCs, while only indirectly affecting GSCs. Loss of Hh signaling in CySCs results in premature differentiation and consequent loss of the cells. Overactivation of the pathway leads to an increased proliferation and an expansion of the cyst stem cell compartment. As Hh signaling is also a regulator of the somatic cells in the mammalian testis and the Drosophila ovary this may reflect a higher degree of homology between these systems than previously expected.

All multicellular organisms constantly need to replace aged or damaged cells. This vital task of tissue homeostasis is fulfilled by stem cells. The balance between self-renewal and differentiation of the stem cell is crucial for this task and tightly regulated by a signaling microenvironment termed the niche. A widely used model for studying stem cell niche biology is the Drosophila testis, where two stem cell populations, the germline stem cells (GSCs) and the somatic cyst stem cells (CySCs), reside in a niche located at the apical tip. A lot is known about the signals regulating GSC maintenance in the testicular niche. It is, however, unknown how the spatial regulation of these signals defines the range of the niche. Here I show, that Bone Morphogenetic Protein (BMP) signaling is specifically activated at the interface of niche and stem cells. This local activation is achieved by coupling the transport of adhesion and signaling molecules in the niche cells and directing their transport to contact sites of niche and stem cells. Localized niche signaling at junctions underlies the so called stem-cell-niche synapse hypothesis proposed for the mammalian hematopoietic stem cell niche. I have shown that disrupting the localized transport causes premature differentiation and stem cell loss. BMP signaling between niche and GSCs therefore provides the first description of a stem-cell-niche synapse and will yield valuable insights into mammalian stem cell biology. The CySCs reside in the niche of the testis together with the GSCs. To understand how the niche maintains both stem cell types in a concerted way, it is essential to know the pathways regulating both stem cell types. Here I show that Hedgehog (Hh) signaling is a key stem cell factor of CySCs, while only indirectly affecting GSCs. Loss of Hh signaling in CySCs results in premature differentiation and consequent loss of the cells. Overactivation of the pathway leads to an increased proliferation and an expansion of the cyst stem cell compartment. As Hh signaling is also a regulator of the somatic cells in the mammalian testis and the Drosophila ovary this may reflect a higher degree of homology between these systems than previously expected.